CpG Islands: Areas of increased density of the dinucleotide sequence cytosine--phosphate diester--guanine. They form stretches of DNA several hundred to several thousand base pairs long. In humans there are about 45,000 CpG islands, mostly found at the 5' ends of genes. They are unmethylated except for those on the inactive X chromosome and some associated with imprinted genes.DNA Methylation: Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.Islands: Tracts of land completely surrounded by water.Dinucleoside Phosphates: A group of compounds which consist of a nucleotide molecule to which an additional nucleoside is attached through the phosphate molecule(s). The nucleotide can contain any number of phosphates.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.Azacitidine: A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels.Epigenesis, Genetic: A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.Sulfites: Inorganic salts of sulfurous acid.Rhode IslandIndian Ocean Islands: Numerous islands in the Indian Ocean situated east of Madagascar, north to the Arabian Sea and east to Sri Lanka. Included are COMOROS (republic), MADAGASCAR (republic), Maldives (republic), MAURITIUS (parliamentary democracy), Pemba (administered by Tanzania), REUNION (a department of France), and SEYCHELLES (republic).Pacific Islands: The islands of the Pacific Ocean divided into MICRONESIA; MELANESIA; and POLYNESIA (including NEW ZEALAND). The collective name Oceania includes the aforenamed islands, adding AUSTRALIA; NEW ZEALAND; and the Malay Archipelago (INDONESIA). (Webster's New Geographical Dictionary, 1988, p910, 880)DNA (Cytosine-5-)-Methyltransferase: An enzyme that catalyzes the transfer of a methyl group from S-ADENOSYLMETHIONINE to the 5-position of CYTOSINE residues in DNA.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.DNA Modification Methylases: Enzymes that are part of the restriction-modification systems. They are responsible for producing a species-characteristic methylation pattern, on either adenine or cytosine residues, in a specific short base sequence in the host cell's own DNA. This methylated sequence will occur many times in the host-cell DNA and remain intact for the lifetime of the cell. Any DNA from another species which gains entry into a living cell and lacks the characteristic methylation pattern will be recognized by the restriction endonucleases of similar specificity and destroyed by cleavage. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms.Genome, Human: The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.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.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.Methylation: Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed)DNA, Neoplasm: DNA present in neoplastic tissue.Genes, Tumor Suppressor: Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.Genes, p16: Tumor suppressor genes located on human chromosome 9 in the region 9p21. This gene is either deleted or mutated in a wide range of malignancies. (From Segen, Current Med Talk, 1995) Two alternatively spliced gene products are encoded by p16: CYCLIN-DEPENDENT KINASE INHIBITOR P16 and TUMOR SUPPRESSOR PROTEIN P14ARF.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.Prince Edward Island: An island in the Gulf of St. Lawrence constituting a province of Canada in the eastern part of the country. It is very irregular in shape with many deep inlets. Its capital is Charlottetown. Discovered by the French in 1534 and originally named Ile Saint-Jean, it was renamed in 1799 in honor of Prince Edward, fourth son of George III and future father of Queen Victoria. (From Webster's New Geographical Dictionary, 1988, p981 & Room, Brewer's Dictionary of Names, 1992, p433)Mediterranean Islands: Scattered islands in the Mediterranean Sea. The chief islands are the Balearic Islands (belong to Spain; Majorca and Minorca are among these), Corsica (belongs to France), Crete (belongs to Greece), CYPRUS (a republic), the Cyclades, Dodecanese and Ionian Islands (belong to Greece), MALTA (a republic), Sardinia and SICILY (belong to Italy). (From Webster's New Geographical Dictionary, 1988, p747)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.Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids.Transcription Initiation Site: The first nucleotide of a transcribed DNA sequence where RNA polymerase (DNA-DIRECTED RNA POLYMERASE) begins synthesizing the RNA transcript.Deoxyribonuclease HpaII: One of the Type II site-specific deoxyribonucleases (EC It recognizes and cleaves the sequences C/CGG and GGC/C at the slash. HpaII is from Haemophilus parainfluenzae. Several isoschizomers have been identified. EC 3.1.21.-.Long Interspersed Nucleotide Elements: Highly repeated sequences, 6K-8K base pairs in length, which contain RNA polymerase II promoters. They also have an open reading frame that is related to the reverse transcriptase of retroviruses but they do not contain LTRs (long terminal repeats). Copies of the LINE 1 (L1) family form about 15% of the human genome. The jockey elements of Drosophila are LINEs.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).Cell Line, Tumor: A cell line derived from cultured tumor cells.Genomic Imprinting: The variable phenotypic expression of a GENE depending on whether it is of paternal or maternal origin, which is a function of the DNA METHYLATION pattern. Imprinted regions are observed to be more methylated and less transcriptionally active. (Segen, Dictionary of Modern Medicine, 1992)Cyclin-Dependent Kinase Inhibitor p16: A product of the p16 tumor suppressor gene (GENES, P16). It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. This protein is produced from the alpha mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced beta transcript, is TUMOR SUPPRESSOR PROTEIN P14ARF. Both p16 gene products have tumor suppressor functions.Epigenomics: The systematic study of the global gene expression changes due to EPIGENETIC PROCESSES and not due to DNA base sequence changes.United States Virgin Islands: A group of islands in the Lesser Antilles in the West Indies, the three main islands being St. Croix, St. Thomas, and St. John. The capital is Charlotte Amalie. Before 1917 the U.S. Virgin Islands were held by the Danish and called the Danish West Indies but the name was changed when the United States acquired them by purchase.5-Methylcytosine: A methylated nucleotide base found in eukaryotic DNA. In ANIMALS, the DNA METHYLATION of CYTOSINE to form 5-methylcytosine is found primarily in the palindromic sequence CpG. In PLANTS, the methylated sequence is CpNpGp, where N can be any base.Melanesia: The collective name for the islands of the Pacific Ocean northeast of Australia, including NEW CALEDONIA; VANUATU; New Hebrides, Solomon Islands, Admiralty Islands, Bismarck Archipelago, FIJI, etc. Melanesia (from the Greek melas, black + nesos, island) is so called from the black color of the natives who are generally considered to be descended originally from the Negroid Papuans and the Polynesians or Malays. (From Webster's New Geographical Dictionary, 1988, p748 & Room, Brewer's Dictionary of Names, 1992, p344)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.Oligonucleotide Array Sequence Analysis: Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.Cyclin-Dependent Kinase Inhibitor p15: An INK4 cyclin-dependent kinase inhibitor containing four ANKYRIN-LIKE REPEATS. INK4B is often inactivated by deletions, mutations, or hypermethylation in HEMATOLOGIC NEOPLASMS.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.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.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.Micronesia: The collective name for islands of the Pacific Ocean east of the Philippines, including the Mariana, PALAU, Caroline, Marshall, and Kiribati Islands. (From Webster's New Geographical Dictionary, 1988, p761 & Room, Brewer's Dictionary of Names, 1992, p350)Oligodeoxyribonucleotides: A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.Glutathione S-Transferase pi: A glutathione transferase that catalyzes the conjugation of electrophilic substrates to GLUTATHIONE. This enzyme has been shown to provide cellular protection against redox-mediated damage by FREE RADICALS.Genes, Neoplasm: Genes whose abnormal expression, or MUTATION are associated with the development, growth, or progression of NEOPLASMS.Chromatin: The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.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 Composition: The relative amounts of the PURINES and PYRIMIDINES in a nucleic acid.Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.Geography: The science dealing with the earth and its life, especially the description of land, sea, and air and the distribution of plant and animal life, including humanity and human industries with reference to the mutual relations of these elements. (From Webster, 3d ed)Death-Associated Protein Kinases: A family of calcium/calmodulin-dependent PROETIN-SERINE-THREONINE KINASES. They are ubiquitously expressed in adult and embryonic mammalian tissues, and their functions are tightly related to the early stages of eukaryotic programmed cell death.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.Channel Islands: A group of four British islands and several islets in the English Channel off the coast of France. They are known to have been occupied prehistorically. They were a part of Normandy in 933 but were united to the British crown at the time of the Norman Conquest in 1066. Guernsey and Jersey originated noted breeds of cattle. (From Webster's New Geographical Dictionary, 1988, p242)Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.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.Reunion: One of the Indian Ocean Islands, east of Madagascar. Its capital is Saint-Denis. It was discovered in 1507 by the Portuguese and claimed by France in 1638. It was first colonized in 1662 as Isle de Bourbon but renamed Reunion in 1793. In 1946 it was made an overseas department of France. The name commemorates the reunion of the revolutionaries from Marseilles with the National Guard in Paris in 1792. (From Webster's New Geographical Dictionary, 1988, p1011; Room, Brewer's Dictionary of Names, 1992, p454; French Embassy)Falkland Islands: A British colony in the Atlantic Islands, comprising two principal islands, East Falkland and West Falkland. Its capital is Stanley. Discovered in 1592, it was not occupied until the French settled there briefly in 1764. Later the English settled there but were expelled by the Spanish in 1770. The Falklands were claimed by Argentina but were occupied in 1833 by the British who, after an April 1982 invasion by Argentina, regained them in June. The islands were named by British Captain John Strong in 1690 for the fifth Viscount Falkland who financed Strong's expedition. The Spanish name for the islands, Malvinas, is from the French Malouins, inhabitants of St. Malo who attempted to colonize the islands in 1764. (From Webster's New Geographical Dictionary, 1988, p389 & Room, Brewer's Dictionary of Names, 1992, p182)Polynesia: The collective name for the islands of the central Pacific Ocean, including the Austral Islands, Cook Islands, Easter Island, HAWAII; NEW ZEALAND; Phoenix Islands, PITCAIRN ISLAND; SAMOA; TONGA; Tuamotu Archipelago, Wake Island, and Wallis and Futuna Islands. Polynesians are of the Caucasoid race, but many are of mixed origin. Polynesia is from the Greek poly, many + nesos, island, with reference to the many islands in the group. (From Webster's New Geographical Dictionary, 1988, p966 & Room, Brewer's Dictionary of Names, 1992, p426)Alu Elements: The Alu sequence family (named for the restriction endonuclease cleavage enzyme Alu I) is the most highly repeated interspersed repeat element in humans (over a million copies). It is derived from the 7SL RNA component of the SIGNAL RECOGNITION PARTICLE and contains an RNA polymerase III promoter. Transposition of this element into coding and regulatory regions of genes is responsible for many heritable diseases.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.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.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.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.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.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.Core Binding Factor Alpha 3 Subunit: A transcription factor that dimerizes with the cofactor CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain.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).Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Chromosomes, Human, Pair 21: A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Genome: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.X Chromosome: The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Toll-Like Receptor 9: A pattern recognition receptor that binds unmethylated CPG CLUSTERS. It mediates cellular responses to bacterial pathogens by distinguishing between self and bacterial DNA.DNA-Cytosine Methylases: Methylases that are specific for CYTOSINE residues found on DNA.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.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.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.Cadherins: Calcium-dependent cell adhesion proteins. They are important in the formation of ADHERENS JUNCTIONS between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (E- for epithelial, N- for neural, and P- for placental cadherins) or by numbers (cadherin-12 or N-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body.Stomach Neoplasms: Tumors or cancer of the STOMACH.Chromatin Immunoprecipitation: A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing.Acetylation: Formation of an acetyl derivative. (Stedman, 25th ed)Colonic Neoplasms: Tumors or cancer of the COLON.Tumor Markers, Biological: Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.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.Blotting, Southern: A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.5' Flanking Region: The region of DNA which borders the 5' end of a transcription unit and where a variety of regulatory sequences are located.Genetic Variation: Genotypic differences observed among individuals in a population.Methyl-CpG-Binding Protein 2: A DNA-binding protein that interacts with methylated CPG ISLANDS. It plays a role in repressing GENETIC TRANSCRIPTION and is frequently mutated in RETT SYNDROME.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Adenine Phosphoribosyltransferase: An enzyme catalyzing the formation of AMP from adenine and phosphoribosylpyrophosphate. It can act as a salvage enzyme for recycling of adenine into nucleic acids. EC 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.Genomics: The systematic study of the complete DNA sequences (GENOME) of organisms.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.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 enzymes