Mutations in the genes BRCA1, BRCA2 or PIK3CA have important implications in the cellular DNA repair mechanisms, and are associated with sensitivity and improved response to platinum-based chemotherapy and PAPR inhibitors. (unilabs.ch)
Homologous recombination (HR) is generally considered the most faithful DSB repair pathway, as it uses the intact sister chromatid as a donor, and it is highly dependent on breast cancer associated genes BRCA1 and BRCA2. (encyclopedia.pub)
The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). (lookformedical.com)
The aim of this study was to determine the frequency of germline variants in BRCA1, BRCA2, CDH1, PALB2, PTEN and TP53 in patients admitted to a medical genetics clinic with breast cancer and to assess these identified variants according to published genetic, surgical and oncological perspectives. (eurjbreasthealth.com)
The exonic regions and exon-intron junctions in BRCA1, BRCA2, CDH1, PALB2, PTEN and TP53 genes were sequenced. (eurjbreasthealth.com)
This study may provide new insights into risk assessment for variants in CDH1, PALB2, PTEN and TP53 , in addition to BRCA1 and BRCA2 , which may prove useful for clinical management of breast cancer patients. (eurjbreasthealth.com)
The purpose of this study was to determine the frequency of germline variants in BRCA1, BRCA2, CDH1, PALB2, PTEN and TP53 in a population of Turkish patients admitted to a medical genetics clinic with breast cancer. (eurjbreasthealth.com)
The most common cause of hereditary breast cancer is because of inherited germline mutations in the high-penetrant cancer predisposition genes BRCA1 and BRCA2 . (eurjbreasthealth.com)
The prevalence of BRCA1 and BRCA2 pathogenic variants is estimated to be 1/400 to 1/500 in the general population and is increased in some populations due to the founder effect (2). (eurjbreasthealth.com)
It is estimated that the risk of developing breast cancer by age of 80 is 72% for BRCA1 mutation carriers and 69% for BRCA2 mutation carriers, respectively. (eurjbreasthealth.com)
According to the literature, the risk for contralateral breast cancer 20 years after first breast cancer diagnosis is 40% for BRCA1 and 26% for BRCA2 carriers (3). (eurjbreasthealth.com)
Recognizing that inherited BRCA1/2 mutations are implicated in the cause of disease in a proportion of EOC patients, has led to the identification of the role of these genes in DNA repair. (biomedcentral.com)
Somatic5
Cancer is a wide collection of different pathologies characterized by an uncontrolled cellular growth and proliferation which is driven by genetic changes that are either acquired (somatic) and usually sequential ("driver" and "passenger" mutations), or inherited. (unilabs.ch)
The first mutation of RB1 in cases of retinoblastoma can be either constitutional or somatic, whereas the second mutation is always somatic. (medscape.com)
In contrast, both mutations in nonhereditary retinoblastoma are somatic. (medscape.com)
Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not. (lookformedical.com)
Somatic mutations in facial skin from countries of contrasting skin cancer risk. (cdc.gov)
Susceptibility3
Since the time of this discovery, two of the three variants (a deletion in the kinase domain in exon 10 and a missense mutation in the FHA domain in exon 3) have been linked to inherited susceptibility to breast as well as other cancers. (wikipedia.org)
Pancreatic cancer is the third most common cancer related to early-onset gene mutation in breast cancer (BRCA, breast cancer susceptibility genes) as well as ovarian cancer. (biomedcentral.com)
Beside these genes, advances in DNA sequencing techniques, such as next generation sequencing, have helped to identify additional breast cancer susceptibility genes, including TP53, CDH1, PALB2 and PTEN and various rare gene variants have also been reported to increase the risk of developing breast cancer. (eurjbreasthealth.com)
Cancers5
These genes and biological processes may help understand the mechanism for inhibiting LINC00958 in cancers. (researchsquare.com)
Mutations to the CHEK2 gene have been linked to a wide range of cancers. (wikipedia.org)
Passenger mutations are additional mutations found in the cancers that do not contribute to cancer proliferation. (medscape.com)
The 11 genes with a high frequency of mutation differed between cancers, and mutations in many DNA DSB repair E3 ligase genes were related to a higher total mutation burden. (bmbreports.org)
Although germline TP53 mutations are rare and seen in approximately 1% of all breast cancers, the lifetime risk of breast cancer in TP53 mutation carriers is nearly 80-90%, considerably greater than for other genes (4). (eurjbreasthealth.com)
Genetic7
Our Core Cancer panels consist of essential gene sets that provide necessary information for genetic tumor biomarker profiling at the molecular level. (unilabs.ch)
In this study, ML techniques were used to investigate the relationship between genetic variations affecting more than 60 candidate genes and carboplatin-induced, taxane-induced, and bevacizumab-induced toxicities in 171 patients with ovarian cancer enrolled in the MITO-16A/MaNGO-OV2A trial. (bvsalud.org)
Genetic drivers are mutations or fusions that confer a survival advantage to "drive" malignant proliferation. (medscape.com)
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. (lookformedical.com)
Molecular characterization and identification of mutations have important implications for predictive, preventive, and personalized medicine, including genetic counseling and development of specific treatment protocols. (eurjbreasthealth.com)
Germline TP53 mutations are associated with Li-Fraumeni syndrome, a rare autosomal dominant genetic disorder. (eurjbreasthealth.com)
In this study, we systematically screened the coding exons of steroid hormone receptor coactivator and corepressor genes in a multiethnic panel of women with breast cancer in an attempt to identify and catalogue potentially functional coding polymorphisms that may serve as genetic markers of breast cancer risk. (biomedcentral.com)
Germline mutations1
1999) discovered three CHEK2 germline mutations among four Li-Fraumeni syndrome (LFS) and 18 Li-Fraumeni-like (LFL) families. (wikipedia.org)
CHEK211
CHEK2 (Checkpoint kinase 2) is a tumor suppressor gene that encodes the protein CHK2, a serine-threonine kinase. (wikipedia.org)
The CHEK2 gene is located on the long (q) arm of chromosome 22 at position 12.1. (wikipedia.org)
The CHEK2 protein encoded by the CHEK2 gene is a serine threonine kinase. (wikipedia.org)
Beyond initial speculations, screening of LFS and LFL patients has revealed no or very rare individual missense variants in the CHEK2 gene. (wikipedia.org)
The evidence from these studies has suggests that CHEK2 is not a predisposition gene to Li-Fraumeni syndrome. (wikipedia.org)
Inherited mutations in the CHEK2 gene have been linked to certain cases of breast cancer. (wikipedia.org)
The CHEK2*1100del mutation is most commonly seen in individuals of Eastern and Northern European descent. (wikipedia.org)
Within these populations the CHEK2*1100delC mutation is seen in 1 out of 100 to 1 out of 200 individuals. (wikipedia.org)
A CHEK2 mutation known as the I157T variant to the FHA domain in exon 3 has also been linked to breast cancer but at a lower risk than the CHEK2*1100delC mutation. (wikipedia.org)
Two more CHEK2 gene mutations, CHEK2*S428F, an amino-acid substitution to the kinase domain in exon 11 and CHEK2*P85L, an amino-acid substitution in the N-terminal region (exon 1) have been found in the Ashkenazi Jewish population. (wikipedia.org)
Mutations to CHEK2 have been found in hereditary and nonhereditary cases of cancer. (wikipedia.org)
Candidate genes2
This study provides a broad list of candidate genes as potential biomarkers for genomic instability and novel therapeutic targets in cancer. (bmbreports.org)
Our findings suggest that common coding variation in these candidate genes do not make a substantial contribution to breast cancer risk in the general population. (biomedcentral.com)
TP534
According to some comprehensive genomic analyses, four major driver genes have been identified in pancreatic cancer: KRAS, CDKN2A, TP53, and SMAD4. (biomedcentral.com)
Tumor protein p53 ( TP53 ) is one of the most mutated genes in cancer, including breast cancer. (eurjbreasthealth.com)
TP53 is a tumor suppressor gene that encodes tumor protein p53, a transcription factor. (eurjbreasthealth.com)
PTEN1
Mutations that disrupt PTEN function define a condition called PTEN hamartoma syndrome, which also includes Cowden syndrome , Bannayan-Riley-Ruvalcaba syndrome, and Proteus/Proteus-like syndrome. (medscape.com)
Protein10
We then performed the gene enrichment and protein-protein interaction (PPI) network analysis to obtain the interacting map. (researchsquare.com)
The BRCA2 R3052W mutated protein exacerbates genome instability, is unable to rescue homology-directed repair, and fails to complement cell survival following exposure to PARP inhibitors and crosslinking drugs. (frontiersin.org)
Surprisingly, despite anticipated defects in DNA binding or RAD51-mediated DNA strand exchange, the BRCA2 R3052W protein mislocalizes to the cytoplasm precluding its ability to perform any DNA repair functions. (frontiersin.org)
(A) BRCA2 protein schematic depicting domain organization: N-terminus, BRC repeats DNA binding domain (DBD), and C-terminal domain (CTD). (frontiersin.org)
RB1 encodes the protein pRB and was the first tumor suppressor gene to be molecularly defined. (medscape.com)
Paclitaxel protein bound is a microtubular inhibitor (albumin-conjugated formulation) and a natural taxane that prevents depolymerization of cellular microtubules, which results in DNA, RNA, and protein synthesis inhibition. (medscape.com)
Ovarian cancer3
The most prominent target gene is BRCA, in which mutations were first identified in breast cancer and ovarian cancer. (biomedcentral.com)
Mutations of this gene are associated with the formation of HEREDITARY BREAST AND OVARIAN CANCER SYNDROME. (lookformedical.com)
Mutations in this gene predispose humans to breast and ovarian cancer. (lookformedical.com)
Variants4
In total, 58 mutations were identified including 14 novel, previously unreported variants. (eurjbreasthealth.com)
Further studies are needed to identify the common gene variants in the Turkish population and evaluate the pathogenity of VUS. (eurjbreasthealth.com)
Cardiovascular ageing is found to be significantly associated with common or rare variants in genes regulating sarcomere homeostasis, myocardial immunomodulation, and tissue responses to biophysical stress. (cdc.gov)
Cataloging and testing of coding variants in coactivator and corepressor genes should continue and may serve as a valuable resource for investigations of other hormone-related phenotypes, such as inter-individual response to hormonal therapies used for cancer treatment and prevention. (biomedcentral.com)
Biomarkers1
Microarray data validation identified 24 potential gene biomarkers associated with PARPis sensitivity. (biomedcentral.com)
BRCA3
In later studies, RAD52 deficiency has been shown to be synthetically lethal with defects in BRCA genes, making RAD52 an attractive therapeutic target, particularly in the context of BRCA-deficient tumors. (encyclopedia.pub)
For tumor cells with BRCA mutations, HRR loss would result in cell death. (biomedcentral.com)
Pancreatic cancer has also been reported to have a strong relationship with BRCA gene mutations, which indicates that pancreatic cancer patients may benefit from PARP inhibitors. (biomedcentral.com)
Missense1
The BRCA2 germline missense variant, R3052W, resides in the DNA binding domain and has been previously classified as a pathogenic allele. (frontiersin.org)
Tumor cells1
All this means that cancer genes and the mechanisms that allow tumor cells to evade death and invade healthy tissue, have deep evolutionary roots. (biotiny.com)
Allele2
Rather than acting as a simple loss-of-function mutation, R3052W behaves as a dominant negative allele, likely by sequestering RAD51 in the cytoplasm. (frontiersin.org)
(F) Western blot of total cellular lysates from DLD-1 parental cells (these cells express a wild-type allele of BRCA2) stably transfected with R3052W (3 and 5 correspond to two independent clones) full-length 2XMBP-BRCA2 cDNA constructs. (frontiersin.org)
Analyses1
(C) Clonogenic survival analyses of BRCA2 WT versus the two independent R3052W clones after treatment with Olaparib, cisplatin, and mitomycin C. (D) Schematic of I-SceI nuclease-induced DSB HDR luciferase assay. (frontiersin.org)
Genomic1
DNA DSB repair E3 ligase genes are involved in tumor suppressive or oncogenic functions, such as RNF168 and FBXW7, by assisting the functionality of these genomic alterations. (bmbreports.org)
Nuclear1
BRCA2 nuclear localization and export sequences are listed. (frontiersin.org)
Cancer8
Long noncoding RNAs (lncRNAs) regulate a number of physiological and pathological processes, including gene transcription and translation, chromatin modification, cell cycle progression, cell proliferation, and oncogenic and tumor-suppressive signals in cancer 6 . (researchsquare.com)
In the previous study, scientists showed that pulsating polyps carry genes that can cause cancer in humans. (biotiny.com)
Recent research, published in the journal Cancer Cell, reports that scientists have identified and characterized mutated versions of the genes that encoding BCR-ABL, the unregulated enzyme driving the blood cancer chronic myeloid leukemia (CML). (biotiny.com)
A family history of pancreatic cancer is an essential risk factor [ 20 ], and germline BRCA2 mutations comprise the highest proportion of known reasons for inherited pancreatic cancer [ 21 ]. (biomedcentral.com)
DNA damage response-related E3 ligases, such as RNF168, FBXW7, and HERC2, were generated with more than 10% mutation in several cancer cells. (bmbreports.org)
Less understood are a newly recognized group of cancer-prone syndromes that are associated with mutations that lengthen telomeres. (cdc.gov)
Global gene expression comparison of 6 PARPi-resistant and 6 PARPi-sensitive 3D AsPCs was indicative for the predominant downregulation of numerous genes and networks with previously demonstrated roles in EOC chemoresistance, suggesting that the PARPis-sensitive AsPCs could display enhanced sensitivity to other chemotherapeutic drugs, commonly applied in cancer management. (biomedcentral.com)
Given the established role of estrogens in breast cancer, we hypothesized that coding variation in steroid receptor coactivator and corepressor genes may alter inter-individual response to estrogen and serve as markers of breast cancer risk. (biomedcentral.com)
Exon1
Additionally, the deletion in the kinase domain on exon 10 has been found rare among LFS/LFL patients. (wikipedia.org)
Passenger1
[ 1 ] Mutations found in pediatric malignancies can be categorized broadly into driver mutations and passenger mutations. (medscape.com)
Proliferation1
Tumor suppressor genes encode proteins that normally provide negative control of cell proliferation. (medscape.com)
Sensitivity2
The BRCA2 R3052W mutation fails to complement chemotherapeutic sensitivity and homology-directed repair functions in BRCA2 knockout cells. (frontiersin.org)
Overexpression of R3052W in DLD1 parental BRCA2 wild-type cells confers sensitivity to MMC DNA damage. (frontiersin.org)
COSMIC1
Mutation and expression frequencies of these genes were analyzed in COSMIC and TCGA. (bmbreports.org)
Transcription1
PARP enzymes are involved in normal cellular function (eg, DNA transcription and repair). (medscape.com)
Apoptosis1
Subsequently, they sequenced the tumorous hydra's DNA and discovered a gene that halts apoptosis, and the activity of which runs amok in tumor tissue. (biotiny.com)
Proteins1
Cellular response to estrogens is mediated through estrogen receptors (ERα and ERβ), which upon binding to ligand and DNA hormone response elements, recruit coactivator and corepressor proteins that regulate the expression of steroid hormone target genes. (biomedcentral.com)
(B) Western blot of total cellular lysates from DLD-1 BRCA2 −/− cells stably transfected with full-length BRCA2 cDNA constructs: BRCA2 Wild Type (WT) and BRCA2 R3052W (1 and 2 correspond to two independent clones). (frontiersin.org)
Damage1
In this study, we sought to determine how R3052W alters the cellular functions of BRCA2 in the DNA damage response. (frontiersin.org)
Mechanistically, EPB41L4A-AS2, acting at least in part as a tumor suppressor, upregulated tumor suppressor gene expression. (cancerindex.org)
The study will compare gene expression differences between blistered and non-blistered skin from individuals with all subtypes of EB, as well as normal skin from non-EB subjects. (stanford.edu)