Genes, APC: Tumor suppressor genes located in the 5q21 region on the long arm of human chromosome 5. The mutation of these genes is associated with familial adenomatous polyposis (ADENOMATOUS POLYPOSIS COLI) and GARDNER SYNDROME, as well as some sporadic colorectal cancers.Adenomatous Polyposis Coli: A polyposis syndrome due to an autosomal dominant mutation of the APC genes (GENES, APC) on CHROMOSOME 5. The syndrome is characterized by the development of hundreds of ADENOMATOUS POLYPS in the COLON and RECTUM of affected individuals by early adulthood.Adenomatous Polyposis Coli Protein: A negative regulator of beta-catenin signaling which is mutant in ADENOMATOUS POLYPOSIS COLI and GARDNER SYNDROME.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Germ-Line Mutation: Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Frameshift Mutation: A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.beta Catenin: A multi-functional catenin that participates in CELL ADHESION and nuclear signaling. Beta catenin binds CADHERINS and helps link their cytoplasmic tails to the ACTIN in the CYTOSKELETON via ALPHA CATENIN. It also serves as a transcriptional co-activator and downstream component of WNT PROTEIN-mediated SIGNAL TRANSDUCTION PATHWAYS.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.Adenoma: A benign epithelial tumor with a glandular organization.Fibromatosis, Aggressive: A childhood counterpart of abdominal or extra-abdominal desmoid tumors, characterized by firm subcutaneous nodules that grow rapidly in any part of the body but do not metastasize. The adult form of abdominal fibromatosis is FIBROMATOSIS, ABDOMINAL. (Stedman, 25th ed)Intestinal Neoplasms: Tumors or cancer of the INTESTINES.Colorectal Neoplasms: Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.Polymorphism, Single-Stranded Conformational: Variation in a population's DNA sequence that is detected by determining alterations in the conformation of denatured DNA fragments. Denatured DNA fragments are allowed to renature under conditions that prevent the formation of double-stranded DNA and allow secondary structure to form in single stranded fragments. These fragments are then run through polyacrylamide gels to detect variations in the secondary structure that is manifested as an alteration in migration through the gels.Fibromatosis, Abdominal: A relatively large mass of unusually firm scarlike connective tissue resulting from active participation of fibroblasts, occurring most frequently in the abdominal muscles of women who have borne children. The fibroblasts infiltrate surrounding muscle and fascia. (Stedman, 25th ed)Pedigree: The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.Intestinal Polyps: Discrete abnormal tissue masses that protrude into the lumen of the INTESTINE. A polyp is attached to the intestinal wall either by a stalk, pedunculus, or by a broad base.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Colonic Neoplasms: Tumors or cancer of the COLON.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Duodenal Neoplasms: Tumors or cancer of the DUODENUM.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.DNA, Neoplasm: DNA present in neoplastic tissue.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Wnt Proteins: Wnt proteins are a large family of secreted glycoproteins that play essential roles in EMBRYONIC AND FETAL DEVELOPMENT, and tissue maintenance. They bind to FRIZZLED RECEPTORS and act as PARACRINE PROTEIN FACTORS to initiate a variety of SIGNAL TRANSDUCTION PATHWAYS. The canonical Wnt signaling pathway stabilizes the transcriptional coactivator BETA CATENIN.Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).Genes, p53: Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.Genes, ras: Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.Mutation Rate: The number of mutations that occur in a specific sequence, GENE, or GENOME over a specified period of time such as years, CELL DIVISIONS, or generations.Microsatellite Repeats: A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Cell Transformation, Neoplastic: Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.Microsatellite Instability: The occurrence of highly polymorphic mono- and dinucleotide MICROSATELLITE REPEATS in somatic cells. It is a form of genome instability associated with defects in DNA MISMATCH REPAIR.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Polyps: Discrete abnormal tissue masses that protrude into the lumen of the DIGESTIVE TRACT or the RESPIRATORY TRACT. Polyps can be spheroidal, hemispheroidal, or irregular mound-shaped structures attached to the MUCOUS MEMBRANE of the lumen wall either by a stalk, pedunculus, or by a broad base.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Sulindac: A sulfinylindene derivative prodrug whose sulfinyl moiety is converted in vivo to an active NSAID analgesic. Specifically, the prodrug is converted by liver enzymes to a sulfide which is excreted in the bile and then reabsorbed from the intestine. This helps to maintain constant blood levels with reduced gastrointestinal side effects.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Anaphase-Promoting Complex-Cyclosome: An E3 ubiquitin ligase primarily involved in regulation of the metaphase-to-anaphase transition during MITOSIS through ubiquitination of specific CELL CYCLE PROTEINS. Enzyme activity is tightly regulated through subunits and cofactors, which modulate activation, inhibition, and substrate specificity. The anaphase-promoting complex, or APC-C, is also involved in tissue differentiation in the PLACENTA, CRYSTALLINE LENS, and SKELETAL MUSCLE, and in regulation of postmitotic NEURONAL PLASTICITY and excitability.Ubiquitin-Protein Ligase Complexes: Complexes of enzymes that catalyze the covalent attachment of UBIQUITIN to other proteins by forming a peptide bond between the C-terminal GLYCINE of UBIQUITIN and the alpha-amino groups of LYSINE residues in the protein. The complexes play an important role in mediating the selective-degradation of short-lived and abnormal proteins. The complex of enzymes can be broken down into three components that involve activation of ubiquitin (UBIQUITIN-ACTIVATING ENZYMES), conjugation of ubiquitin to the ligase complex (UBIQUITIN-CONJUGATING ENZYMES), and ligation of ubiquitin to the substrate protein (UBIQUITIN-PROTEIN LIGASES).Colon: The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON.Codon, Nonsense: An amino acid-specifying codon that has been converted to a stop codon (CODON, TERMINATOR) by mutation. Its occurance is abnormal causing premature termination of protein translation and results in production of truncated and non-functional proteins. A nonsense mutation is one that converts an amino acid-specific codon to a stop codon.Homozygote: An individual in which both alleles at a given locus are identical.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.Mice, Inbred C57BLProto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Precancerous Conditions: Pathological processes that tend eventually to become malignant. (From Dorland, 27th ed)Adenocarcinoma: A malignant epithelial tumor with a glandular organization.Genes, Recessive: Genes that influence the PHENOTYPE only in the homozygous state.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Intestinal Mucosa: Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Genes, Dominant: Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.Genetic Testing: Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Suppression, Genetic: Mutation process that restores the wild-type PHENOTYPE in an organism possessing a mutationally altered GENOTYPE. The second "suppressor" mutation may be on a different gene, on the same gene but located at a distance from the site of the primary mutation, or in extrachromosomal genes (EXTRACHROMOSOMAL INHERITANCE).Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Apc5 Subunit, Anaphase-Promoting Complex-Cyclosome: A subunit of the anaphase-promoting complex whose primary function is to provide structural support for the catalytic and substrate-recognition modules of the complex. Apc5, along with Apc4, tethers the tetratricopeptide-coactivator binding subcomplex to the main structural subunit, Apc1.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome: The largest subunit of the anaphase-promoting complex. It acts primarily as a scaffold for the proper organization and arrangement of subunits. The C-terminal region of Apc1 contains a series of tandem amino acid repeats that are also seen in the 26S proteasome regulatory particle, and may assist with forming and stabilizing protein-protein interactions.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Genetic Complementation Test: A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Apc2 Subunit, Anaphase-Promoting Complex-Cyclosome: Together with the Apc11 subunit, forms the catalytic core of the E3 ubiquitin ligase anaphase-promoting complex (APC-C). Its N-terminus has cullin domains which associate with the RING FINGER DOMAINS of Apc11. Apc2 also interacts with the E2 ubiquitin ligases involved in APC-C ubiquitination reactions.Founder Effect: A phenomenon that is observed when a small subgroup of a larger POPULATION establishes itself as a separate and isolated entity. The subgroup's GENE POOL carries only a fraction of the genetic diversity of the parental population resulting in an increased frequency of certain diseases in the subgroup, especially those diseases known to be autosomal recessive.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Mutant Proteins: Proteins produced from GENES that have acquired MUTATIONS.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Syndrome: A characteristic symptom complex.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Genetic Linkage: The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome: A highly evolutionarily conserved subunit of the anaphase-promoting complex (APC-C) containing multiple 34-amino-acid tetratricopeptide repeats. These domains, also found in Apc subunits 6, 7, and 8, have been shown to mediate protein-protein interactions, suggesting that Apc3 may assist in coordinating the juxtaposition of the catalytic and substrate recognition module subunits relative to co-activators and APC-C inhibitors.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Bacterial Proteins: Proteins found in any species of bacterium.Consanguinity: The magnitude of INBREEDING in humans.Genes, Lethal: Genes whose loss of function or gain of function MUTATION leads to the death of the carrier prior to maturity. They may be essential genes (GENES, ESSENTIAL) required for viability, or genes which cause a block of function of an essential gene at a time when the essential gene function is required for viability.Apc11 Subunit, Anaphase-Promoting Complex-Cyclosome: Together with the Apc2 subunit, forms the catalytic core of the E3 ubiquitin ligase, anaphase-promoting complex-cyclosome. It has a RING H2 domain which interacts with the cullin domain of Apc2. Apc11 also interacts with the E2 ubiquitin ligases involved in APC-C ubiquitination reactions.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Heterozygote Detection: Identification of genetic carriers for a given trait.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Proto-Oncogene Proteins B-raf: A raf kinase subclass found at high levels in neuronal tissue. The B-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.Cdc20 Proteins: Highly conserved proteins that specifically bind to and activate the anaphase-promoting complex-cyclosome, promoting ubiquitination and proteolysis of cell-cycle-regulatory proteins. Cdc20 is essential for anaphase-promoting complex activity, initiation of anaphase, and cyclin proteolysis during mitosis.Mutagenesis, Insertional: Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene or extragenic sequence. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. Proviral DNA insertions into or adjacent to a cellular proto-oncogene can interrupt GENETIC TRANSLATION of the coding sequences or interfere with recognition of regulatory elements and cause unregulated expression of the proto-oncogene resulting in tumor formation.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Genes, BRCA1: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human CHROMOSOME 17 at locus 17q21. Mutations of this gene are associated with the formation of HEREDITARY BREAST AND OVARIAN CANCER SYNDROME. It encodes a large nuclear protein that is a component of DNA repair pathways.Exome: That part of the genome that corresponds to the complete complement of EXONS of an organism or cell.DNA, Mitochondrial: Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.Family Health: The health status of the family as a unit including the impact of the health of one member of the family on the family as a unit and on individual family members; also, the impact of family organization or disorganization on the health status of its members.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Gene Frequency: The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Genetic Variation: Genotypic differences observed among individuals in a population.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Apc10 Subunit, Anaphase-Promoting Complex-Cyclosome: Apc10 is necessary for coactivator-dependent substrate recognition by the anaphase-promoting complex-cyclosome. It binds the Apc2 subunit, which is a part of the catalytic core, and interacts with coactivators Cdh1 or Cdc20 to recruit substrates to the complex.Introns: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.Genes, Bacterial: The functional hereditary units of BACTERIA.Cdh1 Proteins: Cdh1 is an activator of the anaphase-promoting complex-cyclosome, and is involved in substrate recognition. It associates with the complex in late MITOSIS from anaphase through G1 to regulate activity of CYCLIN-DEPENDENT KINASES and to prevent premature DNA replication.Mice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Jews: An ethnic group with historical ties to the land of ISRAEL and the religion of JUDAISM.Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome: A highly conserved subunit of the anaphase-promoting complex (APC-C) containing multiple 34-amino-acid tetratricopeptide repeats. These domains, also found in Apc3, Apc6, and Apc7, have been shown to mediate protein-protein interactions, suggesting that Apc8 may assist in coordinating the juxtaposition of the catalytic and substrate recognition module subunits relative to coactivators and APC-C inhibitors.Kinetics: The rate dynamics in chemical or physical systems.Recombination, Genetic: Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.Crosses, Genetic: Deliberate breeding of two different individuals that results in offspring that carry part of the genetic material of each parent. The parent organisms must be genetically compatible and may be from different varieties or closely related species.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Age of Onset: The age, developmental stage, or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual.Apc7 Subunit, Anaphase-Promoting Complex-Cyclosome: A highly conserved subunit of the anaphase-promoting complex (APC-C) containing multiple 34 amino acid tetratricopeptide repeats. These domains, also found in Apc3, Apc6, and Apc8, have been shown to mediate protein-protein interactions, suggesting that Apc7 may assist in coordinating the juxtaposition of the catalytic and substrate recognition module subunits relative to coactivators and APC-C inhibitors.Drug Resistance, Viral: The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.Genes: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Fungal Proteins: Proteins found in any species of fungus.Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.Genes, Suppressor: Genes that have a suppressor allele or suppressor mutation (SUPPRESSION, GENETIC) which cancels the effect of a previous mutation, enabling the wild-type phenotype to be maintained or partially restored. For example, amber suppressors cancel the effect of an AMBER NONSENSE MUTATION.Eye ProteinsEthylnitrosourea: A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.Polymorphism, Restriction Fragment Length: Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.INDEL Mutation: A mutation named with the blend of insertion and deletion. It refers to a length difference between two ALLELES where it is unknowable if the difference was originally caused by a SEQUENCE INSERTION or by a SEQUENCE DELETION. If the number of nucleotides in the insertion/deletion is not divisible by three, and it occurs in a protein coding region, it is also a FRAMESHIFT MUTATION.Temperature: The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.Genetic Diseases, X-Linked: Genetic diseases that are linked to gene mutations on the X CHROMOSOME in humans (X CHROMOSOME, HUMAN) or the X CHROMOSOME in other species. Included here are animal models of human X-linked diseases.Antigen-Presenting Cells: A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.Penetrance: The percent frequency with which a dominant or homozygous recessive gene or gene combination manifests itself in the phenotype of the carriers. (From Glossary of Genetics, 5th ed)Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Genes, Fungal: The functional hereditary units of FUNGI.Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field.Genes, BRCA2: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human chromosome 13 at locus 13q12.3. Mutations in this gene predispose humans to breast and ovarian cancer. It encodes a large, nuclear protein that is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev 2000;14(11):1400-6)Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.Evolution, Molecular: The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.RNA Splicing: The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.RNA Splice Sites: Nucleotide sequences located at the ends of EXONS and recognized in pre-messenger RNA by SPLICEOSOMES. They are joined during the RNA SPLICING reaction, forming the junctions between exons.Ubiquitin-Protein Ligases: A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.Selection, Genetic: Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population.Apc4 Subunit, Anaphase-Promoting Complex-Cyclosome: A subunit of the anaphase-promoting complex whose primary function is to provide structural support for the catalytic and substrate-recognition modules of the complex. Apc4, along with Apc5, tethers the tetratricopeptide-coactivator binding subcomplex to the main structural subunit, Apc1.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.DNA Repair: The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.ras Proteins: Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 184.108.40.206.Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.Abnormalities, MultipleDrosophila melanogaster: A species of fruit fly much used in genetics because of the large size of its chromosomes.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.BRCA2 Protein: A large, nuclear protein, encoded by the BRCA2 gene (GENE, BRCA2). Mutations in this gene predispose humans to breast and ovarian cancer. The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev. 2000;14(11):1400-6)Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Cercopithecus aethiops: A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.Cell Line, Tumor: A cell line derived from cultured tumor cells.Mitosis: A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.Eye Abnormalities: Congenital absence of or defects in structures of the eye; may also be hereditary.Asian Continental Ancestry Group: Individuals whose ancestral origins are in the southeastern and eastern areas of the Asian continent.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesDrosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.Genetic Heterogeneity: The presence of apparently similar characters for which the genetic evidence indicates that different genes or different genetic mechanisms are involved in different pedigrees. In clinical settings genetic heterogeneity refers to the presence of a variety of genetic defects which cause the same disease, often due to mutations at different loci on the same gene, a finding common to many human diseases including ALZHEIMER DISEASE; CYSTIC FIBROSIS; LIPOPROTEIN LIPASE DEFICIENCY, FAMILIAL; and POLYCYSTIC KIDNEY DISEASES. (Rieger, et al., Glossary of Genetics: Classical and Molecular, 5th ed; Segen, Dictionary of Modern Medicine, 1992)DNA Transposable Elements: Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom.Codon, Terminator: Any codon that signals the termination of genetic translation (TRANSLATION, GENETIC). PEPTIDE TERMINATION FACTORS bind to the stop codon and trigger the hydrolysis of the aminoacyl bond connecting the completed polypeptide to the tRNA. Terminator codons do not specify amino acids.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Genetic Association Studies: The analysis of a sequence such as a region of a chromosome, a haplotype, a gene, or an allele for its involvement in controlling the phenotype of a specific trait, metabolic pathway, or disease.
... mutations of APC initiate most cases of colon and rectal cancers. They also showed how APC functions - through binding to beta- ... "APC mutations occur early during colorectal tumorigenesis". Nature. 359: 235-7. doi:10.1038/359235a0. PMID 1528264. Su LK, ... This gene, called APC, was responsible for Familial Adenomatous Polyposis (FAP), a syndrome associated with the development of ... March 1994). "Mutation of a mutL homolog in hereditary colon cancer". Science. 263: 1625-9. doi:10.1126/science.8128251. PMID ...
The complex (APC-DQ-glaidin) thus stimulates the gliadin specific T-cells to divide. These cells cause B-cells that recognize ... Studies to date have revealed no mutation that would increase risk for MICA. HLA-DQ proteins present polypeptide regions of ... See: Underlying conditions) The APC bearing DQ-gliadin peptide on the surface can bind to T-cells that have an antibody-like T- ... The resulting structure can be presented by APC (with the same gliadin recognizing DQ isoforms) to T-cells, and B-cells can ...
Such mutations and epigenetic alterations can give rise to cancer (see malignant neoplasms). Germ line mutations in DNA repair ... These include APC, CDKN1A, CDKN2A, CDKN2B, Ezrin, FGFR1, GADD45A, MGMT, STK3, STK4, PTEN, RASSF1A, WIF1, as well as several ... Mutation rates are strongly increased in cells with mutations in DNA mismatch repair or in homologous recombinational repair ( ... Also see Mutation frequencies in cancers.) By comparison, the mutation frequency in the whole genome between generations for ...
When APC does not have an inactivating mutation, frequently there are activating mutations in beta catenin. Mutations in APC ... Mutations in APC or β-catenin must be followed by other mutations to become cancerous; however, in carriers of an APC ... inactivating mutation in the APC gene. More than 800 mutationsin the APC gene have been identified in families ... The most common mutation in familial adenomatous polyposis is a deletion of five bases in the APC gene. This mutation changes ...
Later, new knock-out mutants of the Apc gene were engineered. A truncating mutation at codon 716 (ApcΔ716) results in a mouse ... In this model mutation in the Cdx2 gene in the ApcΔ716 mouse model shifted the formation of the polyps from the intestine to ... It was found to carry a truncation mutation at codon 850 of the Apc gene. The Min mouse can develop up to 100 polyps in the ... Further analysis of the APC gene revealed the existence of various mutations in cancer sufferers that also play a role in the ...
APC) protein, encoded by the tumour-suppressing APC gene. Therefore, genetic mutation of the APC gene is also strongly linked ... Somatic mutations of APC in colorectal cancer are also not uncommon. Beta-catenin and APC are among the key genes (together ... Similar mutations are also frequently seen in the β-catenin recruiting motifs of APC. Hereditary loss-of-function mutations of ... APC is like a huge "Christmas tree": with a multitude of β-catenin binding motifs (one APC molecule alone possesses 11 such ...
Most colorectal cancer cases are found with mutations in the APC gene. However, in cases where APC gene is not mutated, ... Mutations in VHL prevent degradation of HIF and thus lead to the formation of hypervascular lesions and renal tumors. The BRCA1 ... Mutations in Fbw7 have been found in more than 30% of human tumors, characterizing is as a tumor suppressor protein. Oncogenic ... A frameshift mutation in ubiquitin B can result in a truncated peptide missing the C-terminal glycine. This abnormal peptide, ...
APC mutations have been linked to certain other cancers such as thyroid cancer. As the mutation causing FAP is genetic, it can ... of cases are a de novo mutation, and of those with an apparent de novo APC mutation (i.e. no known family history) 20% have ... but other tumor-suppressor functions of APC may be related to cell adherence and cytoskeleton organization. Mutation of APC ... Further mutations (e.g., in p53 or kRAS) to APC-mutated cells are much more likely to lead to cancer than they would in non- ...
Mutations in this gene are associated with infantile malignant osteopetrosis. T cell Co-stimulation MHC class II CTLA-4 ... HLA-DRα2 and TIRC7 co-localize at the APC-T cell interaction site. In vivo, triggering the HLA-DR-TIRC7 pathway in ... 2000). "Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosis". Hum. Mol. Genet. 9 ( ...
Hirschman BA, Pollock BH, Tomlinson GE (August 2005). "The spectrum of APC mutations in children with hepatoblastoma from ... Also beta-catenin mutations have been shown to be common in sporadic hepatoblastomas, occurring in as many as 67% of patients. ... Anna CH, Sills RC, Foley JF, Stockton PS, Ton TV, Devereux TR (June 2000). "Beta-catenin mutations and protein accumulation in ...
Oncogene mutations, in contrast, generally involve a single allele because they are gain-of-function mutations. There are ... Other examples of tumor suppressors include pVHL, APC, CD95, ST5, YPEL3, ST7, and ST14. Anticancer gene Metastasis suppressor ... He recognized that this was consistent with a recessive mutation involving a single gene, but requiring biallelic mutation. ... for example mutations in HNPCC, MEN1 and BRCA. Furthermore, increased mutation rate from decreased DNA repair leads to ...
"Reduction in alkaline sphingomyelinase in colorectal tumorigenesis is not related to the APC gene mutation". Int J Colorectal ...
... is associated with high levels of beta-catenin caused by either a mutation in the APC gene or a stabilizing ... "Pilomatricoma-Like Changes in the Epidermoid Cysts of Gardner Syndrome with an APC Gene Mutation". The Journal of Dermatology. ... mutation in the beta-catenin gene, CTNNB1. High levels of beta-catenin increases cell proliferation, inhibit cell death, and ...
"Somatic mutation of the APC gene in gastric cancer: frequent mutations in very well differentiated adenocarcinoma and signet- ... Somatic mutations of the APC gene have also been implicated in the development of gastric SRCCs. The role of other risk factors ... Some cases are inherited, and these cases are often caused by mutations in the CDH1 gene, which encodes the important cell-cell ... "E-Cadherin Gene Mutations in Signet Ring Cell Carcinoma of the Stomach". Japanese Journal of Cancer Research. 87 (8): 843-848. ...
How do missense mutations in the tumor suppressor protein APC lead to cancer?". Molecular Cancer. 10: 101. doi:10.1186/1476- ... stability Effects of mutations on fraction folded & stability (e.g. point mutation/missense mutations) Kinetic protein ... Applications range from biotechnology to study of point mutations and ligand binding assays. FASTpp has been used to probe: ...
The Wnt/APC signal pathway also plays an important role in the regulation of KLF4 expression. LOH, point mutations in the ... Naturally occurring human mutations in the KLF1 gene have been associated with de-repression of the fetal globin gene. KLF2 ( ... "Erythroid phenotypes associated with KLF1 mutations". Haematologica. 96 (5): 635-638. doi:10.3324/haematol.2011.043265. PMC ...
... most frequently by mutations in structurally disordered regions of APC, overexpression of Wnt ligands, loss of inhibitors and/ ... how do missense mutations in the tumor suppressor protein APC lead to cancer?" (PDF). Molecular Cancer. 10: 101. doi:10.1186/ ... Mutations in Wnt signaling-associated transcription factors, such as TCF7L2, are linked to increased susceptibility. Signal ... This accumulation may be due to factors such as mutations in β-catenin, deficiencies in the β-catenin destruction complex, ...
Familial adenomatous polyposis (FAP) is a familial cancer syndrome caused by mutations in the APC gene. In this disorder ... The APC gene is a tumor suppressor and its product is involved in many cellular processes. Inactivation of the APC gene leads ... It is caused by genetic mutations in the Von Hippel-Lindau tumor suppressor gene. The VHL protein (pVHL) is involved in ... Initiation is where the first genetic mutation occurs in a cell. Promotion is the clonal expansion (repeated division) of this ...
"Messing up disorder: how do missense mutations in the tumor suppressor protein APC lead to cancer?" (PDF). Molecular Cancer. ... Presently, it is unclear how exactly the CK1ε-tau mutation results in a shorter free-running period. The CK1ε-tau mutation in ... Therefore, while the mutation to the human Per2 gene results in a similarly shortened period as in the CK1ε-tau hamsters, the ... In humans, mutations affecting the PER2 phosphorylation site of the CK1ε gene results in Familial advanced sleep phase syndrome ...
... the abnormality is a mutation in the APC gene, resulting in its inactivity. Attenuated FAP can occur from other mutations in ... Li J, Woods SL, Healey S, Beesley J (5 May 2016). "Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal ... This condition has been recently characterized by a point mutation in exon 1B of APC gene. Sporadic FGPs have been associated ... Both the β-catenin gene and the APC gene are involved in the same cell growth signalling pathway, but the APC gene is known to ...
Protein S is a cofactor of APC both work to degrade factor V and factor VIII. It has been suggested that Zn2+ might be ... Mutations in this condition change amino acids, which in turn disrupts blood clotting. Functional protein S is lacking, which ... GG frameshift mutation in a family with mixed type I/type III protein S deficiency". Haematologica. 91 (8): 1151-2. PMID ... In terms of the cause of protein S deficiency it can be in inherited via autosomal dominance.A mutation in the PROS1 gene ...
A native antigen is an antigen that is not yet processed by an APC to smaller parts. T cells cannot bind native antigens, but ... However, the vast majority of mutations within expressed genes do not produce neoantigens that are recognized by autologous T ... Another potential filter examines whether the mutation is expected to improve MHC binding. The nature of the central TCR- ... A large fraction of human tumor mutations are effectively patient-specific. Therefore, neoantigens may also be based on ...
Mutations in the TFAP2A gene cause Branchio-oculo-facial syndrome often with a midline cleft lip. In a family with branchio- ... In vivo gene delivery of AP-2 alpha suppressed spontaneous intestinal polyps in the Apc(Min/+) mouse. AP-2 alpha also functions ... Mutations in the AP-2 alpha gene also cause branchio-oculo-facial syndrome, which has overlapping features with Van der Woude ... Mutations in IRF6 gene cause Van der Woude syndrome (VWS) that is a rare mendelian clefting autossomal dominant disorder with ...
This differs from most colorectal cancer, which arises from mutations starting with inactivation of the APC gene. Multiple SSAs ...
Since this amino acid is normally the cleavage site for aPC, the mutation prevents efficient inactivation of factor V. When ... Mutation of this gene-a single nucleotide polymorphism (SNP) is located in exon 10. As a missense substitution of base G to ... Activated protein C (aPC) is a natural anticoagulant that acts to limit the extent of clotting by cleaving and degrading factor ... In both methods, the time it takes for blood to clot is decreased in the presence of the factor V Leiden mutation. This is done ...
Mutations in the LMNA gene encoding lamin A/C. Hum. Mutat. December 2000, 16 (6): 451-9. PMID 11102973. doi:10.1002/1098-1004( ... Mutations in the LMNA gene are associated with several diseases, including Emery-Dreifuss muscular dystrophy, familial partial ... The role of lamins and mutations of LMNA gene in physiological and premature aging]. Postepy Biochem. 2007, 53 (1): 46-52. PMID ... Hutchinson-Gilford progeria syndrome: clinical findings in three patients carrying the G608G mutation in LMNA and review of the ...
... but no extraintestinal manifestations may have non-truncating mutations of the APC gene or mutation in a gene other than APC or ... In patients without identified APC gene mutation, linkage to the APC gene was found in one large family (lod = 5.1, theta 0.01 ... The site of APC gene mutation is associated with pigmented ocular fundus lesions (codons 542-1309) and predisposition to ... METHODS: Mutations of the APC gene were compared with the occurrence of seven extraintestinal manifestations in 475 FAP ...
... end of the APC gene. Methods - Thirty one at risk or affected members from four families with a mutation in the APC gene ... end of the APC gene. Methods - Thirty one at risk or affected members from four families with a mutation in the APC gene ... end of the APC gene. Methods - Thirty one at risk or affected members from four families with a mutation in the APC gene ... end of the APC gene. Methods - Thirty one at risk or affected members from four families with a mutation in the APC gene ...
Most APC mutations are nonsense or frameshift mutations that cause premature truncation of the APC protein.. The likelihood of ... APC gene mutation variantsEdit. The APC is a tumour suppressor gene responsible for the production of adenomatous polyposis ... APC mutations have been linked to certain other cancers such as thyroid cancer. As the mutation causing FAP is autosomal ... 2000]; 9 of 12 individuals had APC mutations identified proximal to the mutation cluster region (codons 1286-1513). General ...
APC mutations in colorectal tumours from FAP patients are selected for CtBP-mediated oligomerization of truncated APC. Jean ... apc *APC products*Apc products*beta-catenin products*gamma-catenin products*arm products*Ras products*sgg products*Apc2 *TCF7L2 ... Beta-catenin degradation mediated by the CID domain of APC provides a model for the selection of APC mutations in colorectal, ... Crystal structure of a beta-catenin/APC complex reveals a critical role for APC phosphorylation in APC function. Yi Xing. ...
The high penetrance of APC mutations, especially in gut epithelium, supports the idea that APC may be involved in a number of ... Thus mutations in APC lead to the accumulation of β-catenin, which causes changes in differentiation, and they also produce ... A unique feature of colon cancer is that truncation mutations in the APC (adenomatous polyposis coli) gene are common to most ... The function of APC in cytoskeletal organization is related to its effect on microtubules and F-actin. Depleting APC from ...
03/15/1999 - "We also examined the role of adenomatous polyposis coli gene (Apc) gene mutations in the GI tumors of Mlh1 mutant ... 01/09/2001 - "Truncation mutations in the adenomatous polyposis coli protein (APC) are responsible for familial polyposis, a ... 12/03/1996 - "The human EBI protein has been cloned by virtue of its interaction with the C-terminus of the APC (adenomatous ... 07/15/1994 - "The adenomatous polyposis coli protein (APC) is mutated in familial adenomatous polyposis patients as well as in ...
... ,ARUP Laboratories is a national reference laboratory and a worldwide leader in innovative ... Achondroplasia Mutation. 9. Achondroplasia Mutation, Fetal. 10. Apolipoprotein B Mutation Detection. 11. Apolipoprotein ... APC Resistance Profile. 6. APC Resistance Profile with Reflex to Factor V Leiden. 7. Protein C Resistance. 8. ... Coatest APC Resistance Kit. 2. Coatest APC Resistance V Kit. 3. Activated Protein C Resistance. 4. Antimicrobial Susceptibility ...
... contained a mutated APC gene. Furthermore, the APC gene met two criteria of importance for tumour initiation. First, mutations ... APC mutations occur early during colorectal tumorigenesis.. Powell SM1, Zilz N, Beazer-Barclay Y, Bryan TM, Hamilton SR, ... We have attempted to determine if mutations of the APC gene play such a role in human colorectal tumours, which evolve from ... These data provide strong evidence that mutations of the APC gene play a major role in the early development of colorectal ...
... as well as somatic mutations in tumors developed in digestive organs (stomach, pancreas, colon, and rectum). Those results ... Several investigators have reported germline mutations of the APC gene in patients with familial adenomatous polyposis (FAP) ... provide evidence that inactivation of the APC gene p … ... Mutations of the APC (adenomatous polyposis coli) gene Hum ... APC mutations have led to some interesting observations. First, the great majority of the mutations found to date would result ...
APC mutations lead to loss of β-catenin regulation, altered cell migration and chromosome instability. They have been ...
APC mutations lead to loss of β-catenin regulation, altered cell migration and chromosome instability. They have been ... APC * NCI-H1581 [H1581] (ATCC® CRL-5878™) ATCC® Number: CRL-5878™ Organism: Homo sapiens, human ...
Mutations in the APC gene and their implications for protein structure and function.. Polakis P1. ... An enormous number of germline and somatic mutations have been identified in the APC tumor suppressor gene. Nearly all of these ... mutations result in premature polypeptide chain termination, but the consequences to APC protein function are unknown. Recent ... and the identification of a microtubule-binding domain in the carboxy-terminal region of APC, are beginning to provide some ...
Generation and Analysis of Mouse Intestinal Tumors and Organoids Harboring APC and K-Ras Mutations. ... Generation and Analysis of Mouse Intestinal Tumors and Organoids Harboring APC and K-Ras Mutations. In: Eferl R., Casanova E. ( ... current laboratory protocols to generate and analyze intestinal tumors and organoids harboring APC and K-Ras double mutations. ...
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The rate of occurrence of serrated adenoma in the study was 30 times that in the general population so APC mutation may ... All three patients with serrated adenomas had mutations in the adenomatous polyposis coli (APC) gene-two proximal to the site ... The APC gene was screened by PCR of DNA from blood leucocytes and the protein truncation test. Complementary DNA was ... Mutations in the other patients were located between codons 554 and 1324. ...
Somatic mutations of the APC gene in colorectal tumors : mutation cluster region in the APC gene MIYOSHI Y. ... Somatic mutation of the APC gene in gastric cancer: frequent mutations in very well differentiated adenocarcinoma and signet- ... Frequent Somatic Mutations of the APC and p53 Genes in Sporadic Ampullary Carcinomas * * IMAI Yasuo ... Mutations in the APC gene and their implications for protein structure and function POLAKIS P. ...
Effects of APC mutations on CRT. (A) Schematic of wild-type (WT) and mutant APC. APC is a 2843-aa protein (23) that contains ... exogenous WT APC comigrated with the endogenous APC. In SW480 cells, APC1309Δcomigrated with the endogenous mutant APC. In all ... J. Med. 325, 37 (1991) and at least 85% of these tumors contain APC mutations [(13); Y. Miyoshi, et al., Hum. Mol. Genet. 1, ... Mutations of the APC gene are the most common disease-causing genetic events in humans; about 50% of the population will ...
APC mutations have been detected at a relatively high frequency in gastric tumors of Japanese patients, yet such mutations have ... for mutations in the APC gene between codons 686 and 1693 using the protein truncation test. Although 19 truncating mutations ... This suggests that in relation to APC mutations gastric adenocarcinomas from Brazilian patients are similar to those that occur ... Detection of microsatellite instability but not truncating APC mutations in gastric adenocarcinomas in Brazilian patients. ...
Sulindac increases colonic tumors in mice with Apc, Mlh1 and Apc/Mlh1 mutations.. Osamu Itano, Naoto Kurihara, Kunhua Fan, ... Sulindac increases colonic tumors in mice with Apc, Mlh1 and Apc/Mlh1 mutations. ... Sulindac increases colonic tumors in mice with Apc, Mlh1 and Apc/Mlh1 mutations. ... Sulindac increases colonic tumors in mice with Apc, Mlh1 and Apc/Mlh1 mutations. ...
Since the development of the first mouse model with a germline Apc mutation in the early 1990s, twenty other Apc mouse and rat ... Rodent models with various Apc mutations have enabled experimental validation of different Apc functions in tumors and normal ... Zeineldin, M., & Neufeld, K. L. (2013). Understanding phenotypic variation in rodent models with germline Apc mutations. Cancer ... Adenomatous Polyposis Coli (APC) is best known for its crucial role in colorectal cancer suppression. ...
Conditional mutations of beta-catenin and APC reveal roles for canonical Wnt signaling in lens differentiation.. [Gemma ... To activate Wnt/beta-catenin signaling, beta-catenin (Catnb) and adenomatous polyposis coli (Apc) genes were conditionally ...
Apc-associated intestinal tumor formation appears to require functional loss of both Apc alleles. Apc has, therefore, been ... Apc Gene Mutation Is Associated with a Dominant-Negative Effect upon Intestinal Cell Migration. Najjia N. Mahmoud, Susan K. ... In mice bearing a germ-line Apc mutation, we found that enterocyte β-catenin expression was also increased in histologically ... Apc Gene Mutation Is Associated with a Dominant-Negative Effect upon Intestinal Cell Migration ...
Elevated incidence of polyp formation in APC(Min/⁺)Msh2⁻/⁻ mice is independent of nitric oxide-induced DNA mutations.. [ ... Indeed, we found that the MMR pathway repairs nitric oxide-induced DNA mutations in cell lines. To test whether nitric oxide ... However, nitric oxide also has genotoxic effects to host cells by producing mutations that can predispose to colon cancer ... These data show that nitric oxide and iNOS do not promote colon cancer in APC(Min/+)Msh2(-/-) mice. ...
... for mutations in the APC gene. A mutation was detected in only one of the 35 samples (3%). This mutation, present in a primary ... Mutation of the APC gene is responsible for colorectal tumors in which ras and p53 mutations are also often involved. Using PCR ... This study clarified that APC gene mutations are not largely involved in the development of clinical prostate cancer. ... Although ras and p53 gene mutations have been detected in some prostate cancers, the major genetic alterations involved in its ...
However, loss of Pten in the context of Apc deficiency accelerates tumorigenesis through increased activation of Akt, leading ...
GenesFamilialBeta-cateninPolyposisCancersPolypsCommonlyGenesMismatch repairAdenomasOncogenicCodonPhenotypesTumoursGermline and somatic mutationsDeletionAlleleMUTYHGeneticTumorigenesisPoint mutationsAdenomaProtein truncation testColon CancerProteinsCaused by inherited mutationsTruncationMutantsDetectableGene Mutation Is AssociatedOccurCodonsDeleterious mutationsCluster regionFrameshift mutationsAnaphase-promoting complexNonsenseDevelop colorectalSporadic colorectal cancerOncogeneTumor CellsFound in 39AFAPGuanine nucleoLocalization
- The root cause of FAP is understood to be a genetic mutation -a flaw in the body's tumour suppressor genes that prevent development of tumours. (wikipedia.org)
- Constitutive transcription of Tcf target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium. (labome.org)
- Three variants are known to exist, FAP and attenuated FAP (originally called hereditary flat adenoma syndrome ) are caused by APC gene defects on chromosome 5 while autosomal recessive FAP (or MYH-associated polyposis ) is caused by defects in the MUTYH gene on chromosome 1. (wikipedia.org)
- International polyposis registries exists that track known cases of FAP or APC gene defects, for research and clinical purposes. (wikipedia.org)
- Human tumorigenesis is associated with the accumulation of mutations both in oncogenes and in tumour suppressor genes. (nih.gov)
- The protein products of mutant APC genes present in colorectal tumors were found to be defective in this activity. (sciencemag.org)
- Furthermore, colorectal tumors with intact APC genes were found to contain activating mutations of β-catenin that altered functionally significant phosphorylation sites. (sciencemag.org)
- To activate Wnt/beta-catenin signaling, beta-catenin (Catnb) and adenomatous polyposis coli (Apc) genes were conditionally mutated in two Cre lines that are active in whole lens (MLR10) or only in differentiated fibers (MLR39), from E13.5. (sigmaaldrich.com)
- In pedigrees without identified APC gene mutation, analysis of linkage to chromosome 5q and/or assessment of neoplasms for replication errors characteristic of mutation in mismatch repair genes were performed. (bmj.com)
- CONCLUSIONS: Patients with the colorectal phenotype of FAP but no extraintestinal manifestations may have non-truncating mutations of the APC gene or mutation in a gene other than APC or mismatch repair genes. (bmj.com)
- The aim of this study was to characterize, by peptidomic and genetic approaches, 4 pa-tients that, although at the colonoscopy showed many polyps, they did not present any mutations of APC and MutYH genes (defined here unresolved FAP). (unipd.it)
- Variation in polyp development is controlled, an appreciable extent, by genetic factors segregating in the Collaborative cross population and suggests that it is suited for identifying modifier genes associated with Apc Min/+ mutation, after assessing sufficient number of lines for quantitative trait loci analysis. (biomedcentral.com)
- It has also been suggested that genomic instability is the initiating event in colorectal tumorigenesis and, if this is true, mutations of DNA mismatch repair (MMR) genes (or at similar loci) are the most likely candidates. (ox.ac.uk)
- In a group of 656 unselected sporadic colorectal cancer patients, aberrations in the APC , K-ras , CTNNB1 genes, and expression of hMLH1 were investigated. (biomedcentral.com)
- Therefore, several of these internal ids could be associated with a single genomic COSV id where the mutation has been mapped to all overlapping genes and transcripts. (sanger.ac.uk)
- APC is a critical component of the Wnt/Wingless signaling pathway, which is disrupted in sporadic cancers (e.g., colorectal adenomas, hepatocellular carcinomas, and medulloblastomas) by somatic mutations affecting multiple genes encoding alternative pathway components, including APC and CTNNB1 (encoding beta-catenin). (cdc.gov)
- Most of the mutated Apc genes in colorectal tumors lack β-catenin-binding regions and fail to inhibit Wnt signaling, leading to overproliferation of tumor cells. (springer.com)
- Analysis of your relation of methylation of all 4 genes with previously published success on APC disrupting occasions uncovered a favourable trend between WIF one and DKK3 methylation and APC mutation. (pdgfreceptor.com)
- The root cause of FAP is understood to be a genetic mutation -a flaw in the body's tumour suppressor genes that prevent development of tumours. (wikipedia.org)
- This method, called the yeast-based protein truncation test (YPTT), is simple and fairly cheap, and it can be applied to any genes that are inactivated by protein truncating mutations. (elsevier.com)
- A pioneer in the field of cancer genomics, his studies on colorectal cancers revealed that they result from the sequential accumulation of mutations in oncogenes and tumor suppressor genes. (wikipedia.org)
- Mutations in the BRCA1 or BRCA2 genes occur more frequently in people of Ashkenazi heritage. (oncolink.org)
- And while we now know that mutations in genes such as ATM and PALB2 also increase breast cancer risk, it's been unclear by how much. (breastcancer.org)
- Mutations in these genes have been linked to a higher risk of breast and ovarian cancer. (breastcancer.org)
- People who have a mutation in one of the genes that code for these factors have an increased risk of blood clots. (labtestsonline.org)
- Molecular analysis of the APC and MUTYH genes in Galician and Catalonian FAP families: a different spectrum of mutations? (biomedcentral.com)
- To gain insight into the role of altered gene expression in hereditary colorectal polyposis predisposition, in the present study we analyzed absolute and allele-specific expression (ASE) of adenomatous polyposis coli ( APC ) and mutY Homolog ( MUTYH ) genes. (biomedcentral.com)
- Twenty-nine patients did not show mutations in both genes. (biomedcentral.com)
- The identification of mechanisms predisposing to hereditary colorectal polyposis is necessary for direct genetic diagnosis of carrier status in cases without detectable mutations in known genes. (biomedcentral.com)
- The genes mostly implicated in the inheritance of adenomatous polyposis, a condition that leads to colorectal cancer, are adenomatous polyposis coli ( APC ) involved in FAP (OMIM #175100) and mutY Homolog ( MUTYH ) involved in MUTYH -associated polyposis (MAP) (OMIM#608456). (biomedcentral.com)
- Detection of germline mutations was performed in Mismatch Repair, APC and MUTYH genes. (hindawi.com)
- Both hemophilia a and b are due to mutations in genes on the x chromosome. (healthtap.com)
- The two genes in which mutations are known to cause algs are jag1 and notch2. (healthtap.com)
- This is a mutation in one of the genes that help to process iron absorption. (healthtap.com)
- A chromosome will contain many genes, so a chromosome mutation will effect many genes. (healthtap.com)
- In the large intestines of MSI1 mutant mice, APC levels and Wnt target genes were unaffected, while proliferation and stem cell populations were decreased. (ku.edu)
- Current data suggest that mutations in p53, DCC and APC tumor suppressor genes contribute to the stepwise progression of anal squamous cell carcinoma in immunocompetent individuals. (genome.jp)
- In the small intestine mice carrying the Apc mutation responded to sulindac with decreased tumor growth, and mice with the mismatch repair mutation responded to sulindac with increased tumor growth. (aacrjournals.org)
- Defects in mismatch repair occur after APC mutations in the pathogenesis of sporadic colorectal tumours. (ox.ac.uk)
- 60 years of age were investigated for MSI, Mismatch Repair proteins expression, KRAS and BRAF mutations, hypermethylation, and LINE-1 hypomethylation. (hindawi.com)
- We have attempted to determine if mutations of the APC gene play such a role in human colorectal tumours, which evolve from small benign tumours (adenomas) to larger malignant tumours (carcinomas) over the course of several decades. (nih.gov)
- Here we report that sequence analysis of 41 colorectal tumours revealed that the majority of colorectal carcinomas (60%) and adenomas (63%) contained a mutated APC gene. (nih.gov)
- First, mutations of this gene were found in the earliest tumours that could be analysed, including adenomas as small as 0.5 cm in diameter. (nih.gov)
- Furthermore, inactivation of both alleles of the APC gene seems to be required as an early event to develop most of adenomas and carcinomas in the colon and rectum as well as some of those in the stomach. (nih.gov)
- In this study, we have analyzed somatic APC point mutations and loss of heterozygosity (LOH) in 133 colorectal adenomas from six FAP patients. (oup.com)
- APC mutations, primarily nonsense mutations and frameshift insertions and deletions encoding truncated proteins, were subsequently identified in a majority of sporadic colorectal adenomas and carcinomas 21 , 22 . (nature.com)
- Somatic mutations lead to malignant transformation of adenomas. (cdc.gov)
- Findings: The prevalence of APC mutations significantly increases with adenoma count while MAP shows a peak prevalence in individuals with 50-99 adenomas. (ssrn.com)
- Interpretation: Adenoma count, age at diagnosis of the adenomas and year of analysis are important predictive factors for APC and MUTYH mutations. (ssrn.com)
- Recently, biallelic mutations in MUTYH have also been identified in patients with multiple colorectal adenomas and in APC -negative patients with FAP. (biomedcentral.com)
- General indications for APC gene testing include patients who themselves have had 10 or more adenomas or have had a desmoid tumor, or patients who have a family member with an APC gene mutation found on genetic testing . (healthtap.com)
- These data establish mTORC1 as a crucial, β-catenin independent effector of oncogenic Apc mutations and highlight the importance of mTORC1 regulation by APC during embryonic development. (biologists.org)
- As such, APC mutation not only compromises tumour suppressor function but may also have oncogenic properties. (biologists.org)
- As such, APC mutation may also have oncogenic properties. (biologists.org)
- It suggests that APC mutation in RPE cells activates first an oncogenic process and, in a second time, a mechanism of tumor suppression that stops lesion progression. (arvojournals.org)
- Oncogenic APC mutations have been well characterized in colorectal carcinoma because they are dominant mutations that drive the development of colorectal cancer. (nature.com)
- To address this issue, we have conditionally expressed an oncogenic K- ras V12 allele in the small intestine of adult mice either alone or in the context of Apc deficiency. (pnas.org)
- In renal epithelium, expression of the oncogenic K- ras V12 allele in the absence of Apc induces the rapid development of renal carcinoma. (pnas.org)
- Thus, overexpression of oncogenic K- ras may yield very different phenotypes to simple mutation. (pnas.org)
- The second mutant, APC1309Δ, is the most common germline APC mutation ( 2 ), a 5-base pair (bp) deletion that produces a frameshift at codon 1309 and truncation of the protein. (sciencemag.org)
- Finally, APC2644Δ represents a germline mutation resulting from a 4-bp deletion in codon 2644. (sciencemag.org)
- Specifically, germline mutations around codon 1300 are associated with allelic loss of the remaining wild-type APC allele while mutations 3′ or 5′ of this region predominantly show a second truncating mutation. (biologists.org)
- Correlation between the development of extracolonic manifestations in FAP patients and mutations beyond codon 1403 in the APC gene. (semanticscholar.org)
- Typical disease symptoms were observed in families who harboured mutations between exon 4 (codon 169) and codon 1393 of exon 15. (semanticscholar.org)
- Attenuated' phenotype has been reported with mutation in the 5' end of the gene (5' to codon 158), but genotype-phenotype relations at the 3' end (3' to codon 1596) have not been described fully. (elsevier.com)
- Methods - Thirty one at risk or affected members from four families with a mutation in the APC gene located at codon 1979 or 2644 were evaluated. (elsevier.com)
- The deletion at codon 1061 was not found in 19 APC -positive Galician patients but represented 23% of the Catalonian positive families (p = 0,058). (biomedcentral.com)
- The results we present indicate that in Galician patients the frequency of the hotspot at codon 1061 in APC differs significantly from the Catalonian and also other Caucasian populations. (biomedcentral.com)
- This article compares and contrasts currently available Apc rodent models with particular emphasis on providing potential explanations for their reported variation in three areas: 1) intestinal polyp multiplicity, 2) intestinal polyp distribution, and 3) extra intestinal phenotypes. (ku.edu)
- APC is a negative regulator of the Wnt pathway and constitutive Wnt activation mediated by enhanced Wnt-β-catenin target gene activation is believed to be the predominant mechanism responsible for Apc mutant phenotypes. (biologists.org)
- However, recent evidence suggests that additional downstream effectors contribute to Apc mutant phenotypes. (biologists.org)
- We hypothesized that truncating Apc mutations should activate mTORC1 in vivo and that mTORC1 plays an important role in Apc mutant phenotypes. (biologists.org)
- Furthermore, mTORC1 activation is essential downstream of APC as mTORC1 inhibition partially rescues Apc mutant phenotypes including early lethality, reduced circulation and liver hyperplasia. (biologists.org)
- hESCs derived RPE cells harboring APC mutation recapitulate the main phenotypes associated to POFLs observed in FAP patients. (arvojournals.org)
- By contrast, HDAC inhibitors and clr6 HDAC mutations rescued temperature sensitive (ts) phenotypes of the mutants of the ubiquitin ligase complex anaphase-promoting complex/cyclosome (APC/C), which display metaphase arrest. (biologists.org)
- Twenty-three germline mutations were identified which gave rise to a variety of different phenotypes. (semanticscholar.org)
- Aims - To describe and compare colorectal and extracolonic phenotypes in a case series of families with mutation in the 3' end of the APC gene. (elsevier.com)
- We found that expression of K- ras V12 does not affect normal intestinal homeostasis or the immediate phenotypes associated with Apc deficiency. (pnas.org)
- A fraction (7-23 %) of APC mutation negative cases with phenotypes overlapping with attenuated FAP (AFAP) or classical FAP, is associated with biallelic germline variants of the MUTYH gene. (biomedcentral.com)
- Second, the frequency of such mutations remained constant as tumours progressed from benign to malignant stages. (nih.gov)
- In addition, approximately 80% of all sporadic colorectal tumours have mutations in APC ( Polakis, 1997 ). (biologists.org)
- and (3) APC mutations in simple repeat sequences [(N)n, (N1N2)n, or (N1N2N3)n] in RER+ tumours. (ox.ac.uk)
- Although it remains possible that MMR is abnormal in tumours from HNPCC families before APC mutations occur, it is likely that in sporadic colon tumours, APC mutations, rather than genomic instability, are the initiating events in tumorigenesis. (ox.ac.uk)
- The early to intermediate stages of the majority of colorectal tumours are thought to be driven by aberrations in the Wnt ( APC , CTNNB1 ) and Ras ( K-ras ) pathways. (biomedcentral.com)
- Mutations at the phosphorylation sites (codons 31, 33, 37, and 45) in the CTNNB1 gene were observed in tumours from only 5/464 patients. (biomedcentral.com)
- Tumours with truncating APC mutations and activating K-ras mutations in codons 12 and 13 occurred at similar frequencies (37% (245/656) and 36% (235/656), respectively). (biomedcentral.com)
- Seventeen percent of tumours harboured both an APC and a K-ras mutation (109/656). (biomedcentral.com)
- Patients harbouring a tumour with absent hMLH1 expression were older, more often women, more often had proximal colon tumours that showed poorer differentiation when compared to patients harbouring tumours with an APC and/or K-ras mutation. (biomedcentral.com)
- Conversely, in tumours lacking these APC mutations [ 7 ], activating missense mutations at one of the phosphorylation sites at codons 31, 33, 37 and 45 of exon 3 of the CTNNB1 gene (encoding the β-catenin protein) can render it stable as it can no longer be tagged for cellular degradation. (biomedcentral.com)
- A mutant of the cohesin loader Mis4 (adherin) was hypersensitive to TSA and synthetically lethal with HDAC deletion mutations. (biologists.org)
- We propose that this selection process is aimed at a specific degree of β-catenin signaling optimal for tumor formation, rather than at its constitutive activation by deletion of all of the β-catenin downregulating motifs in APC. (oup.com)
- Recent in vivo studies using inducible gene deletion have allowed the precise function of Apc in the adult intestine to be defined ( 4 ). (pnas.org)
- The most common mutation in FAP is a deletion of five building blocks of DNA (nucleotides) in the APC gene. (medlineplus.gov)
- We report 20 novel germline APC mutations and 3 large deletions (6%) encompassing the whole-gene deletions and/or exon 14 deletion. (biomedcentral.com)
- Of these, 12 mutations were deletion, one was insertion and 12 were base substitution. (nel.edu)
- We expressed green fluorescent protein (GFP)-fusion proteins with full-length and deletion mutants of Xenopus APC in Xenopus epithelial cells, and observed their dynamic behavior in live cells. (rupress.org)
- Our data suggest that alterations in enterocyte migration occur in cells bearing a single mutant Apc allele, and that sulindac sulfide may normalize enterocyte growth in these cells. (aacrjournals.org)
- We suggest therefore that the initial APC mutation acts as a `double whammy', destabilising the genome and setting the stage for deregulated proliferation upon loss of the second APC allele. (biologists.org)
- Rather, while one allele acquires a truncating mutation, the second allele undergoes either loss of heterozygosity (LOH) or a second truncating mutation ( Kinzler and Vogelstein, 1996 ). (biologists.org)
- Co-inheritance of FV Leiden and quantitative FV deficiency on different alleles, a rare condition known as pseudo-homozygous APC resistance, is associated with pronounced APC resistance and 50% reduced FV levels, because of non-expression of the non-Leiden FV allele. (wiley.com)
- Thrombin generation measurements in FV-deficient plasma reconstituted with purified normal FV and FV Leiden confirmed these observations and showed that the expression of the normal FV allele is an important modulator of APC resistance in FV Leiden heterozygotes. (wiley.com)
- However, allelic losses at 5q21 are frequent in breast and lung carcinomas (6 , 8 , 9) , suggesting that mechanisms other than mutation may inactivate the other allele. (aacrjournals.org)
- FAP is due to a germline mutation in the APC gene or to biallelic variations of MutYH gene. (unipd.it)
- La FAP è causata da una mutazione germinale del gene APC o da varianti bialleliche del gene MutYH. (unipd.it)
- Lo scopo di questo lavoro è stato caratterizzare 4 pazienti in cui, nonostante l'esame colonscopico presentasse una poliposi conclamata, non risultavano mutazioni nei gene APC e MutYH (in questa tesi definiti pazienti FAP irrisolti) utilizzando un approccio integrato di peptidomica e genomica. (unipd.it)
- Methods: All application forms used to send patients in for APC and MUTYH mutation analysis between 1992 and 2017 were collected (n=2082). (ssrn.com)
- Moreover, the chance of finding an APC or MUTYH mutation steadily declined over the past 23 years. (ssrn.com)
- The aim of this work is therefore to determine the frequency of APC and MUTYH mutations among FAP families from two Spanish populations. (biomedcentral.com)
- MUTYH analysis was then conducted in those APC -negative families and in 9 additional patients from a previous study. (biomedcentral.com)
- MUTYH analysis is also recommended for all APC -negative families, even if a recessive inheritance is not confirmed. (biomedcentral.com)
- APC and MUTYH mRNA expression levels were investigated by quantitative Real-Time PCR (qRT-PCR) analysis using TaqMan assay and by ASE assays using dHPLC-based primer extension. (biomedcentral.com)
- Twenty out of 49 patients showed germline mutations: 14 in APC gene and six in MUTYH gene. (biomedcentral.com)
- Results from qRT-PCR indicated that gene expression of both APC and MUTYH was reduced in patients analyzed. (biomedcentral.com)
- APC and MUTYH showed a reduced germline expression, not always corresponding to gene mutation. (biomedcentral.com)
- Expression of APC is decreased in mutation negative cases and this appears to be a promising indicator of FAP predisposition, while for MUTYH gene, mutation is associated to reduced mRNA expression. (biomedcentral.com)
- Although the molecular genetic events that occur in colorectal cancer have been known for many years, the selective advantage conferred by these mutations has remained unclear ( 1 , 2 ). (pnas.org)
- A genetic blood test of the APC gene exists that can determine whether it is present, and therefore can predict the possibility of FAP. (wikipedia.org)
- Some genetic mutations increase a person's risk of developing a cancer. (oncolink.org)
- There are a few genetic mutations found more commonly in the Ashkenazi population, including BRCA 1 & 2, HNPCC and APC. (oncolink.org)
- Finding out about a genetic mutation can be scary. (oncolink.org)
- A genetic error that causes harm is called a mutation. (breastcancer.org)
- For many years, genetic tests only looked for BRCA1 or BRCA2 mutations. (breastcancer.org)
- A study has taken the first step in helping to estimate the relative risk associated with 25 genetic mutations linked to breast and ovarian cancer. (breastcancer.org)
- The researchers then compared and analyzed the genetic test results between the matched pairs of women to estimate the risk of cancer associated with each mutation. (breastcancer.org)
- APC germline mutations were found in 39% of the patients and, despite the great number of genetic variants described so far in this gene, seven new mutations were identified. (biomedcentral.com)
- This study could improve the predictive genetic diagnosis of at-risk individuals belonging to families with reduced mRNA expression regardless of presence of mutation. (biomedcentral.com)
- In genetics, a mutation is a change in the nucleotide sequence of the genome of an organism, virus, or extrachromosomal genetic element. (healthtap.com)
- Can prothrombin genetic mutation be inherited? (healthtap.com)
- Genetic mutations are by definition inherited. (healthtap.com)
- Who needs apc genetic testing? (healthtap.com)
- Is hereditary angioedema type III a genetic mutation? (healthtap.com)
- Pku is a genetic disorder due to mutations in a gene. (healthtap.com)
- The risk of developing cancer is higher in people who are born with certain genetic changes (mutations) that are passed on from their parents and found in every cell in their body. (ahealthyme.com)
- APC mutations occur early during colorectal tumorigenesis. (nih.gov)
- However, loss of Pten in the context of Apc deficiency accelerates tumorigenesis through increased activation of Akt, leading to rapid development of adenocarcinoma. (epfl.ch)
- According to the classical interpretation of Knudson's 'two-hit' hypothesis for tumorigenesis, the two 'hits' are independent mutation events, the end result of which is loss of a tumor suppressing function. (oup.com)
- The roles of the intrinsic mutation rate and genomic instability in tumorigenesis are currently controversial. (ox.ac.uk)
- However, K- ras V12 expression accelerates intestinal tumorigenesis and confers invasive properties after Apc loss over the long term. (pnas.org)
- However, activation of K- ras V12 after Apc loss results in increased tumorigenesis with distinct kinetics. (pnas.org)
- Third, most identified point mutations in the APC gene are transitions from cytosine to other nucleotides. (nih.gov)
- We observed that when germline mutations result in truncated proteins without any of the seven β-catenin downregulating 20-amino-acid repeats distributed in the central domain of APC, the majority of the corresponding somatic point mutations retain one or, less frequently, two of the same 20-amino-acid repeats. (oup.com)
- Notably, and in contrast to previous observations, in a patient where the germline APC mutation retains two such repeats, the majority of the somatic hits are point mutations (and not LOH) located upstream and removing all of the 20-amino-acid repeats. (oup.com)
- The APC gene was screened by PCR of DNA from blood leucocytes and the protein truncation test. (bmj.com)
- We here report the analysis of 40 primary sporadic gastric adenocarcinomas and 35 primary sporadic colon adenocarcinomas (from patients resident in São Paulo, Brazil), for mutations in the APC gene between codons 686 and 1693 using the protein truncation test. (scielo.br)
- Mutation screening was performed using denaturing gradient gel electrophoresis and/or protein truncation test. (biomedcentral.com)
- However, nitric oxide also has genotoxic effects to host cells by producing mutations that can predispose to colon cancer development. (sigmaaldrich.com)
- To test whether nitric oxide promotes colon cancer, we genetically ablated the inducible nitric oxide synthase (iNOS) or inhibited iNOS activity in the APC(Min/+)Msh2(-/-) mouse model of colon cancer. (sigmaaldrich.com)
- These data show that nitric oxide and iNOS do not promote colon cancer in APC(Min/+)Msh2(-/-) mice. (sigmaaldrich.com)
- In addition, colon cancer cells with APC mutations have weakened kinetochore-microtubule interactions. (biologists.org)
- Therefore, to determine whether APC mutations can initiate chromosome instability in human cells, we expressed N-terminal APC fragments in HCT-116 cells, a near diploid colon cancer cell line with two wild-type APC alleles. (biologists.org)
- However, whether truncated APC and topo IIα interact in colon cancer cells remained unknown. (ku.edu)
- Also, longer truncated APC proteins endogenous to colon cancer cell lines interact with topo IIα. (ku.edu)
- Complementary DNA was synthesised by reverse transcription of mRNA from blood leucocytes, amplified by PCR with APC gene primers, and the PCR products translated in vitro and determined as full or truncated proteins by gel electrophoresis. (bmj.com)
- APC homodimerizes through its NH 2 -terminus ( 4 ) and interacts with at least six other proteins: β-catenin ( 5 ), γ-catenin (plakoglobin) ( 6 ), tubulin ( 7 ), EB1 ( 8 ), hDLG, a homolog of the Drosophila Discs Large tumor suppressor protein ( 9 ), and glycogen synthase kinase-3β (GSK-3β) ( 10 ), a mammalian homolog of ZW3 kinase. (sciencemag.org)
- Whether any of these interacting proteins communicate APC growth-controlling signals is unknown. (sciencemag.org)
- If this inhibitory activity is critical for APC's tumor suppressor function, then mutant APC proteins should be defective in this activity. (sciencemag.org)
- The APC protein accomplishes these tasks mainly through association with other proteins, especially those that are involved in cell attachment and signaling. (medlineplus.gov)
- This mutation changes the sequence of the building blocks of proteins (amino acids) in the resulting APC protein. (medlineplus.gov)
- Through its C-terminus, APC binds to post-synaptic density discs large zonula occludens domain-containing proteins, such as discs large (DLG) and post-synaptic density (PSD)-95, and may play important roles in epithelial morphogenesis, brain development and neuronal functions. (springer.com)
- To date, various types of MT-associated proteins have been identified and characterized (for review see Cassimeris 1999 ), but APC protein appeared to be unique in its MT-associated localization only in specialized areas of cells, which would be important for cellular morphogenesis. (rupress.org)
- To evaluate this hypothesis, we tested four APC mutants (Fig. 1 A) for their ability to inhibit β-catenin-Tcf-regulated transcription (CRT) in transfection assays. (sciencemag.org)
- We show that cells expressing N-APC mutants exit mitosis prematurely in the presence of spindle toxins, consistent with a spindle checkpoint defect. (biologists.org)
- Although both motifs contribute to securin ubiquitination by APC/C(Cdh1), securin mutants lacking either motif are efficiently ubiquitinated. (rcsb.org)
- Cytoplasmic granules formed by either overexpression of wild-type Fus or by expression of ALS mutants of Fus preferentially recruit APC-RNPs. (rupress.org)
- An apparent exception to this relationship is found in Schizosaccharomyces pombe mutants with mutations of the anaphase-promoting complex (APC). (asm.org)
- In contrast to this prediction, we show that Cdc2p kinase activity fluctuates in APC cut mutants due to Cdc13/cyclin B destruction. (asm.org)
- In APC-null mutants, however, septation and cutting do not occur and Cdc13p is stable. (asm.org)
- We conclude that APC cut mutants are hypomorphic with respect to Cdc13p degradation. (asm.org)
- Indeed, overproduction of nondestructible Cdc13p prevents septation in APC cut mutants and the normal reorganization of septation initiation network components during anaphase. (asm.org)
- Furthermore, a large number of mutants have been isolated with mutations that affect various aspects of cell division, allowing a detailed understanding of these events to emerge ( 22 , 24 ). (asm.org)
- This suggests that in relation to APC mutations gastric adenocarcinomas from Brazilian patients are similar to those that occur in Europe, and support a fundamental difference both between gastric carcinomas that occur in different geographical regions and between the molecular etiology of gastric and colorectal adenocarcinomas occurring in São Paulo, Brazil. (scielo.br)
- Inactivation of TSGs may occur via multiple mechanisms, including allelic loss, gene mutation, or by methylation of CpG sites in promoter regions. (aacrjournals.org)
- Mutations in the other patients were located between codons 554 and 1324. (bmj.com)
- Expression of pigmented ocular fundus lesions was strongly associated with mutations in codons 541-1309, but no other extraintestinal manifestations were related to mutation position. (bmj.com)
- Multiplicity of extraintestinal manifestations was high with mutation in codons 1465, 1546, and 2621. (bmj.com)
- The two hotspots at codons 1061 and 1309 of the APC gene accounted for 9,4% of the APC -positive families, although they were underrepresented in Galician samples. (biomedcentral.com)
- According to the main results in our sample, 16 alleles with deleterious mutations (80% of the patients) were identified while 7 (35%) patients had no deleterious mutations. (cdc.gov)
- Only TNM stage was associated with the presence of deleterious mutations. (cdc.gov)
- TNM stage I+II in comparison with III+IV, when compared with the patients with no deleterious mutations identified. (cdc.gov)
- Almost all of the APC mutations are nonsense or frameshift mutations, which truncate the APC protein and are thought to inactivate normal APC function. (elsevier.com)
- Direct sequencing, SSCP analysis and TaqMan genotyping were used to identify point and frameshift mutations, meanwhile large rearrangements in the APC gene were screened by multiplex ligation-dependent probe amplification (MLPA). (biomedcentral.com)
- The anaphase-promoting complex/cyclosome (APC/C) promotes anaphase onset and mitotic exit through ubiquitinating securin and cyclin B1. (rcsb.org)
- The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit ubiquitin ligase that mediates the ubiquitination of a multitude of substrates to drive cell cycle progression ( 1 ⇓ - 3 ). (pnas.org)
- Here, we show that Pfkfb3 is absent from neurons in the brain cortex and that Pfkfb3 in neurons is constantly subject to proteasomal degradation by the action of the E3 ubiquitin ligase, anaphase-promoting complex/cyclosome (APC/C)-Cdh1. (sebbm.es)
- En este trabajo se muestra que la Pfkfb3 es un sustrato de la E3 ubiquitina ligasa APC/ C (anaphase-promoting complex/cyclosome), y su cofactor Cdh1, para su ubiquitinación. (sebbm.es)
- There was a predominance of nonsense (45% of the patients) and frameshift (20% of the patients) mutations. (cdc.gov)
- We show a novel method for detecting nonsense and frameshift APC gene mutations by using Saccharomyces cerevisiae. (elsevier.com)
- Widen an APC fragment contains a nonsense or frameshift mutation, HA-tagged truncating APC peptide can be detected by Western blotting using an anti-HA antibody. (elsevier.com)
- The majority of the APC germline mutations are frameshift, nonsense or splice site mutations in the 5'half of the gene resulting in a truncated protein. (biomedcentral.com)
- Recent advances, including the identification of an oligomerization domain, the localization of several beta-catenin binding sites, some of which down-regulate beta-catenin in vivo, and the identification of a microtubule-binding domain in the carboxy-terminal region of APC, are beginning to provide some clues. (nih.gov)
- Henderson BR (2000) Nuclear-cytoplasmic shuttling of APC regulates beta-catenin suncellular localization and turnover. (springer.com)
- Fus is not required for APC-RNP localization but is required for efficient translation of associated transcripts. (rupress.org)
- A. Ryo, M. Nakamura, G. Wulf, Y.-C. Liou, K. P. Lu, Pin1 regulates turnover and subcellular localization of β-catenin by inhibiting its interaction with APC. (sciencemag.org)
- In the patients with novel mutations, correlations of the mutation localization are discussed in context of the classical and/or attenuated phenotype of the disease. (biomedcentral.com)
- In these cells, endogenous APC was localized in clusters of puncta near the ends of MTs at peripheral membrane sites of migrating edges, and this localization required intact MTs. (rupress.org)