• Here, we delineated the possible oncogenic interactions between genes containing germline and somatic mutations in TNBC and non-TNBC and investigated whether there are differences in gene expression and mutation burden between the two types of breast cancer. (hindawi.com)
  • Network and pathway analyses revealed functionally related genes interacting in gene regulatory networks and multiple signalling pathways enriched for germline and somatic mutations for each type of breast cancer. (hindawi.com)
  • The results show that integrative genomics is a powerful approach for delineating oncogenic interactions between genes containing germline and genes containing somatic mutations in TNBC and non-TNBC and establishes putative functional bridges between genetic and somatic alterations and the pathways they control in the two types of breast cancer. (hindawi.com)
  • Gene signatures derived from the genes containing functionally germline variants significantly distinguished recurred and non-recurred patients in two ER+ breast cancer independent cohorts ( n = 200 and 295, P = 1.4 × 10 −3 ). (nature.com)
  • Family history remains one of the major risk factors that contribute to cancer, and recent studies have identified several genes whose germline mutations are associated with cancer. (nature.com)
  • Targeted next-generation sequencing (NGS) of a panel of 80 genes was performed on her initial bone marrow aspirate sample and identified PTPN11, NRAS , and DNMT3A somatic mutations. (frontiersin.org)
  • To date, researchers have already identified germline mutations in 22 specific genes associated with the FA pathway, each accounting for an individual FA complementation group ( 2 ). (frontiersin.org)
  • NEW YORK - Secondary cancer risk appears to jump in pediatric cancer patients carrying risky germline variants in DNA repair genes who are exposed to DNA-damaging treatments such as chemotherapy or radiotherapy as part of their original treatment, new research suggests. (genomeweb.com)
  • By bringing in available medial record information on the patients' past chemotherapy doses and radiotherapy exposures, they found ties between secondary breast cancer risk in women with pathogenic germline mutations in homologous recombination genes, particularly after some chest radiotherapy or anthracycline chemotherapy treatments. (genomeweb.com)
  • The team's analysis also pointed to a rise in sarcoma risk after certain doses of alkylating chemotherapy in the past pediatric cancer patients with germline homologous recombination gene variants, while the cancer survivors with germline changes in genes from a nucleotide excision repair pathway appeared more prone to secondary thyroid cancer or non-melanoma skin cancer after earlier radiotherapy treatments. (genomeweb.com)
  • In total, 20 patients had deleterious and 7 suspected deleterious mutations in BRCA1 or BRCA2 genes. (biomedcentral.com)
  • We also performed a transcriptomics analysis on fibroblasts from different patients carrying TRAF7 mutations, which showed alterations in the expression of different genes that might contribute to the phenotype. (ub.edu)
  • Currently no more than 25-30% of these familial cases can be explained by mutations in the known susceptibility genes, BRCA1 and BRCA2 being the major ones. (oulu.fi)
  • These driver mutations can be single nucleotide variants in cancer driver genes or larger structural rearrangements called mosaic chromosomal alterations (mCAs). (bvsalud.org)
  • 8 Genetic tests based on these highly penetrant gene mutations have shown their usefulness, but they can explain only a small fraction (5-10%) of patients. (nature.com)
  • Background and aim The majority of mismatch repair (MMR) gene mutations causing Lynch syndrome (LS) occur either in MLH1 or MSH2 . (bmj.com)
  • Non-FA (or underlying FA) patients harboring heterozygous germline FA gene mutations may also face an increased risk of developing bone marrow failure, primary immunodeficiency disease, and hereditary cancer predisposition syndromes. (frontiersin.org)
  • This case highlights the importance of genetic counseling in patients with hematopoietic neoplasms with high clinical suspicion for carrying cancer susceptibility gene mutations, which require timely diagnosis and personalized management. (frontiersin.org)
  • Here, we present the case of a 54-year-old female patient with multiple FA gene mutations. (frontiersin.org)
  • (B) The patient was born with four Fanconi anemia (FA) gene mutations and germline predisposition to cancers. (frontiersin.org)
  • Collectively, our findings provide compelling evidence of increased [subsequent neoplasm] risk among childhood cancer survivors with [DNA repair gene] mutations and prior genotoxic treatment exposures," the authors wrote. (genomeweb.com)
  • This study evaluated the TruSight Tumor 170 assay for the simultaneous detection of somatic gene mutations (SNPs and indels), gene fusions and CNVs, and its implementation into routine diagnostics. (mdpi.com)
  • Results: All somatic gene mutations were identified when covered by the assay. (mdpi.com)
  • He also spearheaded an international effort to identify the first Mendelian germline predisposition gene in testicular germ cell tumors, CHEK2, with potentially immediate clinical and mechanistic implications. (the-asci.org)
  • BAP1 tumor predisposition syndrome is caused by mutations in the BAP1 gene. (medlineplus.gov)
  • Her project focused on the genetic variants that contribute to predisposition for and etiology of myeloproliferative neoplasms, or MPNs. (mskcc.org)
  • Germline mutations in the ATM gene cause Ataxia-telangiectasia (A-T), characterized by cerebellar ataxia and cancer predisposition. (nih.gov)
  • The current study is the first evaluating the role of TOPBP1 mutations in familial cancer predisposition. (oulu.fi)
  • We addressed this problem by integrating germline mutation information from genome-wide association studies with somatic mutation information from next-generation sequencing using gene expression data as the intermediated phenotype. (hindawi.com)
  • Achieving that goal requires understanding the germline somatic mutation interaction landscape and discovery of molecular markers driving each disease and distinguishing the two types of breast cancer. (hindawi.com)
  • This suggests that a typical individual possesses ~80 somatic single-nucleotide variants present in ≥2% of cells-comparable to the number of de novo germline mutations per generation-with about half of individuals having at least one potentially function-altering somatic mutation somewhere in the cortex. (nih.gov)
  • In addition to an inherited (germline) mutation in one copy of the gene, which is found in essentially every cell of the body, a second, non-inherited (somatic) mutation usually occurs in the normal copy of the gene in cells that give rise to tumors. (medlineplus.gov)
  • In a genome-wide-association study, she and her lab colleagues, in collaboration with Ross Levine of the Human Oncology and Pathogenesis Program, found a germline susceptibility variant for MPN in JAK2 , a gene known to acquire a somatic mutation in MPN patients. (mskcc.org)
  • Clonal hematopoiesis (CH) is characterized by the acquisition of a somatic mutation in a hematopoietic stem cell that results in a clonal expansion. (bvsalud.org)
  • In a recent study that included 250 high risk Lebanese patients, 14 (5.6%) were found to carry a deleterious BRCA mutation (7 BRCA1, 7 BRCA2) and 31 others (12.4%) carried a variant of uncertain significance (VUS) [ 12 ]. (biomedcentral.com)
  • Hereditary mutations, mostly BRCA1 and BRCA2, contribute to risk, and since up to 50% of patients with ovarian cancer may have a BRCA mutation, all patients should have genetic counseling regarding germline BRCA testing. (jnccn.org)
  • In an exploratory analysis of the final reporting of the ABRAZO trial -a phase 2 study of talazoparib following platinum or multiple cytotoxic regimens in metastatic BRCA1/BRCA2 mutations-among those who received talazoparib after platinum-based therapy, anticancer activity appeared to be greater in patients who were further away from receiving platinum therapy. (medscape.com)
  • She developed ovarian cancer, and then the altered FA pathway plus exposure to cytotoxic drugs promoted the emergence of acquired somatic mutations and the NUP98-HOXC11 fusion, all of which contributed to the development of secondary t-CMML. (frontiersin.org)
  • However, classification of ovarian cancer is evolving beyond BRCA mutations to include molecular data. (jnccn.org)
  • No current screening methods for high-grade ovarian cancer (HGOC) guarantee effective early detection for high-risk women such as germline BRCA mutation carriers. (tau.ac.il)
  • The LCR for breast cancer in women harboring germline mutations in this gene is similar to the risk of carriers of germline mutations in BRCA1 (44 to 68 % until 70 years of age), whereas the risk of ovarian cancer ranges from 11 to 40 % [ 5 - 8 ]. (biomedcentral.com)
  • Altogether 214 Finnish patients having breast and/or ovarian cancer were analysed for germline mutations in the BACH1 gene. (oulu.fi)
  • Mutation analysis of the BARD1 gene among 126 Finnish patients having family history of breast and/or ovarian cancer revealed seven alterations in the protein-encoding region. (oulu.fi)
  • BENTA disease can also arise spontaneously in a patient as the result of a de novo mutations in CARD11, which means that the mutation was not inherited from the parents. (wikipedia.org)
  • For decades, germline mutations, contained within the heritable genome, and somatic mutations, acquired de novo by breast cancer cells, have been considered as separate research endeavours, and each has unique clinical applications and implications for patient care. (hindawi.com)
  • ERCC1 were absent in other low-grade in lowgrade diffuSe glioMaS schwannomas also carried the MSH4 diffuse gliomas and in primary (de novo) germline mutation and, in addition, a glioblastomas (Ohta et al. (who.int)
  • Alterations of the TP53 gene occur not only as somatic mutations in human malignancies, but also as germline mutations in some cancer-prone families such as Li-Fraumeni syndrome. (thermofisher.com)
  • Patients with gemistocytic astrocytoma with oligodendroglial differentiation, IDH1 samples from a Li-Fraumeni family with and secondary glioblastoma with RRAS mutation, and 1p/19q loss, suggesting a TP53 germline mutation and multiple deletion tended to have shorter survival that FUBP1 immunohistochemistry is nervous system tumours revealed times than those without deletion. (who.int)
  • Somatic mutations of TP53 are among the most common in cancer and germline mutations of TP53 (usually missense) can cause Li-Fraumeni syndrome (LFS). (oncotarget.com)
  • We revisited a four-generation LFS family where no TP53 mutation had been identified and found a 445 kb inversion spanning from the TP53 intron 1 towards the centromere. (oncotarget.com)
  • Methods: We have screened 65 Dutch TP53-negative LFS/LFL candidate patients for CHEK2 germline mutations to determine their contribution to the LFS/LFL phenotype. (eur.nl)
  • However, CHEK2 might be a factor contributing to individual tumour development in TP53-negative cancer-prone families. (eur.nl)
  • If a mutation was found in the child's DNA but not their parents', the team surmised this mutation must have been emerged when the sperm and egg came together in the uterus. (newsweek.com)
  • Mutations found in the child's blood DNA that were not present in either parent's blood DNA were then inferred to have originated in the parents' germlines. (neurosciencenews.com)
  • This was demonstrated by the somatic PTEN deletion in parotid tumors in addition to the germline loss of FLCN , thereby following a model of compound heterozygosity, instead of the classic two-hit mutation. (medscape.com)
  • PARP inhibitors have demonstrated clear benefit in patients with BRCA mutated tumors, especially in the first-line setting, and HRD testing can guide their use for patients without BRCA mutations. (jnccn.org)
  • Spectrum of SMARCB1/INI1 mutations in familial and sporadic rhabdoid tumors. (cdc.gov)
  • SMARCB1 mutations in schwannomatosis and genotype correlations with rhabdoid tumors. (cdc.gov)
  • Gastrointestinal stromal tumors (GISTs) are predominantly initiated by KIT mutations. (lu.se)
  • In contrast, germline mutations of the SMARCB1 ( INI1 ) tumor suppressor gene were described in familial and sporadic schwannomatosis patients. (biomedcentral.com)
  • A single normal cell randomly acquires a series of mutations that allows it to proliferate and to be transformed into a cancer cell (i.e., founding clone), which initiates tumor progression and recurrence. (nature.com)
  • Hence, pre-existing germline variants provide a profound constraint on the evolution of tumor founding clones and subclones and therefore have a contingent effect on the genetic makeup of tumor and presumably patient outcomes. (nature.com)
  • We have previously shown that tumor founding clone mutations are able to predict tumor recurrence. (nature.com)
  • Together, the germline and somatic mutations result in a complete loss of BAP1 protein function in tumor cells. (medlineplus.gov)
  • Pineoblastoma is a rare pediatric cancer induced by germline mutations in the tumor suppressors RB1 or DICER1. (elsevierpure.com)
  • Families with mutations in BRCA1/2 differ in terms of age at diagnosis, the number of family members affected, and tumor prognosis [ 9 ]. (biomedcentral.com)
  • Consequently, treatment of mice carrying germline KIT/V558A mutation with DDR1/2 inhibitor significantly impeded tumor growth, and the combined use of DDR1/2 inhibitor and imatinib, the first-line targeted therapeutic agent for GISTs, markedly enhanced tumor growth suppression. (lu.se)
  • Throughout ASCO 2017, experts across a wide range of tumor types and research interests contributed their perspectives on the meeting to Medscape's ASCO 2017 Live Blog . (medscape.com)
  • These mutations do not appear to be associated with T cell malignancies. (wikipedia.org)
  • Research in Urologic Oncology Branch is aimed at identifying the genetic and biochemical defects that contribute to genitourinary malignancies, and to translating these discoveries into safe and effective treatment strategies. (cancer.gov)
  • Following the discovery of oncogenic HGF receptor mutations in kidney cancer, Dr. Bottaro joined the NCI's Urologic Oncology Branch (UOB) in 2003 to study growth factor signaling in urological malignancies and support diagnostic and therapeutic development as Head of the Molecular Therapeutics Facility. (cancer.gov)
  • From 1992 to 2006, 303 patients were referred from the French outpatient genetic clinics for point mutations and genomic rearrangements analysis of the NF2 gene to investigate the presence of schwannomas. (biomedcentral.com)
  • Hence, germline genomic information could be used for developing non-invasive genomic tests for predicting patients' outcomes in breast cancer. (nature.com)
  • New somatic mutations arise and are selected if they confer a selective fitness advantage (e.g., proliferation, survival, etc.) to a founding clone in the context of a pre-existing genomic landscape (i.e., germline variants). (nature.com)
  • My primary research interest lies in investigation of interplay between occurrence of mutations and normal genomic maintenance processes. (ed.ac.uk)
  • Although biallelic NF2 mutations are found in schwannomas, no germ line event is detected in schwannomatosis patients. (biomedcentral.com)
  • All five patients carrying a SMARCB1 mutation had more multiple schwannomas, corresponding to 10.2% of patients with schwannomatosis. (biomedcentral.com)
  • These results suggest that patients with schwannomas have a significant probability of carrying a SMARCB1 mutation. (biomedcentral.com)
  • To improve the clinical indications for SMARCB1 molecular screening in medical genetics practice, we evaluated its implication in a series of patients exhibiting non-vestibular schwannomas and no NF2 germline alteration. (biomedcentral.com)
  • The gain-of-function CARD11 mutations associated with BENTA disease may also predispose patients to B cell malignancy. (wikipedia.org)
  • Furthermore, Rdd-BRCA1 protein expression was detected in recurrent carcinomas from patients who carried germline BRCA1 185delAG mutations. (jci.org)
  • Germline variants such as BRCA1/2 play an important role in tumorigenesis and clinical outcomes of cancer patients. (nature.com)
  • Finally, we found that recurred patients possessed a higher rate of germline variants. (nature.com)
  • 9 Here we reasoned that the collective impact of germline variants in cancer patients might largely determine tumorigenesis, evolution, and even clinical outcomes. (nature.com)
  • Methods From a cohort of 202 LS suspected patients, 13 patients showing loss of PMS2 expression in tumours were screened for germline mutations in PMS2, using a long range PCR based strategy and multiplex ligation dependent probe amplification (MLPA). (bmj.com)
  • Conclusions Pathogenic PMS2 mutations were detected in 69% of patients harbouring LS associated tumours with loss of PMS2 expression. (bmj.com)
  • Patients with FA gene mutation are hypersensitive to DNA damage and unable to successfully repair damaged DNA when exposed to DNA-crosslinking agents, cytotoxic chemotherapeutics, and ionizing radiation ( 3 , 4 ). (frontiersin.org)
  • Throughout the lifetime of patients with an FA gene mutation, DNA damage increasing accumulates, which would lead to a complex clinically and genetically heterogeneous disorder characterized by developmental abnormalities, bone marrow failure (BMF), immune deficiency, and a high risk of developing various cancers (e.g. (frontiersin.org)
  • Further, patients with MLLT1 mutations presented at a younger age and were associated with ILNR rather than PLNR. (nature.com)
  • As we recently reported, analysis of 77 FHWT by whole genome sequencing (WGS, 58 patients) or whole exomic sequencing (WES,19 patients) identified 825 high-quality somatic, non-synonymous variants, with an average of 11 candidate mutations/case (range 2-42) (ref. 6 ). (nature.com)
  • The objective of this pilot study is to evaluate, for the first time, the contribution of germline mutations in BRCA1/2 to breast cancer among Jordanian patients. (biomedcentral.com)
  • Although small, our selected patient cohort shows an important incidence of deleterious and suspected deleterious BRCA1/2 mutations suggesting that genetic testing should be offered to patients with certain high risk features. (biomedcentral.com)
  • We contributed to the delineation of a recently described syndrome caused by germline mutations in TRAF7 by gathering and describing a cohort of 45 patients. (ub.edu)
  • To define the incidence and characteristics of Lynch syndrome-related small-intestinal adenocarcinomas, meticulous familial and clinical histories were obtained from 195 patients with small-intestinal adenocarcinoma, and MMR protein immunohistochemistry, microsatellite instability, MLH1 methylation, and germline mutational analyses were performed. (oncotarget.com)
  • We identify NPM1 germline mutations in patients with dyskeratosis congenita presenting with bone marrow failure and demonstrate that they are deficient in small nucleolar RNA binding. (elsevierpure.com)
  • This study included patients with and without germline BRCA mutations. (medscape.com)
  • On the other side, adding veliparib to chemotherapy did not lead to a statistically significant improvement in progression-free or overall survival in a phase 2 trial of patients with metastatic breast cancer who had germline BRCA1/2 mutations, as reported at the 2016 San Antonio Breast Cancer Symposium. (medscape.com)
  • This phase 3 trial compared olaparib monotherapy 300 mg twice daily versus physician choice chemotherapy in a 2:1 fashion in patients with germline BRCA mutations and HER2- negative metastatic breast cancer. (medscape.com)
  • Molecular alterations long known to contribute to WT development include mutations and/or deletions involving WT1 , WTX , CTNNB1 and loss of imprinting or loss of heterozygosity (LOH) at 11p15 (reviewed in ref. 5 ). (nature.com)
  • A meticulous patient history taking, MMR protein immunolabeling, and germline MMR gene mutational analysis are important for the diagnosis of Lynch syndrome-related small-intestinal adenocarcinomas. (oncotarget.com)
  • We characterize the landscape of somatic mutations-mutations occurring after fertilization-in the human brain using ultra-deep (~250×) whole-genome sequencing of prefrontal cortex from 59 donors with autism spectrum disorder (ASD) and 15 control donors. (nih.gov)
  • My project involved investigation of variability of mutation rates across the non-coding parts of the genome, more specifically, how it is related to the interaction of DNA with proteins, such as transcription factors (TFs). (ed.ac.uk)
  • used genome editing to make mutations in a stretch of DNA that regulates the gene involved in wing vein formation. (elifesciences.org)
  • Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. (nature.com)
  • no MLLT1 -mutant tumours had accompanying WT1 , WTX , DROSHA , DGCR8 , SIX1 , or SIX2 mutations ( Supplementary Table 1 ). (nature.com)
  • We observe a mean of 26 somatic single-nucleotide variants per brain present in ≥4% of cells, with enrichment of mutations in coding and putative regulatory regions. (nih.gov)
  • BENTA stands for "B cell expansion with NF-κB and T cell anergy" and is caused by germline heterozygous gain-of-function mutations in the gene CARD11 (see OMIM entry #607210). (wikipedia.org)
  • Whole-exome sequencing (WES) verified RAD51C, BRIP1, PALB2 , and FANCG heterozygous germline mutations of the FA pathway, which were further confirmed in buccal swab samples by Sanger sequencing. (frontiersin.org)
  • We performed network and pathway analyses to discover molecular networks and signalling pathways enriched for germline and somatic mutations. (hindawi.com)
  • Comprehensive genetic testing showed that many molecular variations (including FA gene germline mutations, RAS and epigenetic pathway somatic mutations, and NUP98-HOXC11 fusion) were highly linked to her serious and complex medical history ( Figures 1A, B ). (frontiersin.org)
  • With increasing use in clinical and public health practices, molecular genetic testing affects persons and their families in every life stage by contributing to disease diagnosis, prediction of future disease risk, optimization of treatment, prevention of adverse drug response, and health assessment and management. (cdc.gov)
  • however, germline genetic variants play a role in tumorigenesis by partaking in critical biological and cellular processes. (hindawi.com)
  • A subgroup of 56 cases exhibiting non-vestibular schwannomas as confirmed by MRI examination at time of diagnosis were selected for SMARCB1 point mutations screening. (biomedcentral.com)
  • Folliculin mutation databases have been established by Wei and colleagues at the National Cancer Institute and by the European BHDS Consortium. (medscape.com)
  • The exact origin of the folliculin mutation remains under investigation. (medscape.com)
  • Scholars@Duke publication: APC promoter hypermethylation contributes to the loss of APC expression in colorectal cancers with allelic loss on 5q. (duke.edu)
  • We report in-frame insertion/deletion MLLT1 mutations in FHWT that are absent in other TARGET paediatric tumour types. (nature.com)
  • A stabilizing mutation rather than deletion of p53 accelerates metastatic dissemination. (elsevierpure.com)
  • As a result, researchers have been able to develop thousands of mouse strains with mutations that mirror those seen in human genetic disease . (yourgenome.org)
  • These data support a model whereby activating MLLT1 mutations early in renal development result in the development of Wilms tumour. (nature.com)
  • We conclude that activating MLLT1 mutations accompanied by Wnt activation early in renal development result in the development of Wilms tumour. (nature.com)
  • Women with the highest mutation rates had significantly fewer live births than other women and were more likely to be younger when they gave birth to their last child. (neurosciencenews.com)
  • useful for glioma diagnosis (Baumgarten additional germline mutations. (who.int)
  • Birt-Hogg-Dubé syndrome is caused by a mutation in the folliculin ( FLCN ) gene that has been mapped to the short arm of chromosome 17, specifically 17p11.2. (medscape.com)
  • Aiming to characterize truncating mutations in MAGEL2, which are responsible for Schaaf-Yang syndrome (SYS), we performed different experiments that suggest a potential toxic effect of the produced truncated form of the protein, which lacks its most relevant functional domain. (ub.edu)
  • Normally, HGF stimulates proliferation, motility and morphogenesis in a wide spectrum of cell types, contributing to embryonic development and to tissue repair in adulthood. (cancer.gov)
  • Mutations were classified as deleterious, suspected deleterious, variant of uncertain significance or favor polymorphisms. (biomedcentral.com)
  • In particularly, I am interested in how interaction of transcriptions factors (TFs) with DNA affects mutation occurrence and accumulation, and contribute to biased retention of potentially functionally important variants in both germline and in cancer. (ed.ac.uk)
  • In a family, each child's risk of inheriting the mutated CARD11 allele is independent of whether or not other siblings inherited the mutation. (wikipedia.org)
  • Thus far, it is unclear to what extent germline variants affect tumorigenesis. (nature.com)
  • I am particularly interested in interplay between mutation occurrence, TF binding, replication and repair, and how this affects heritable variants arising in male germline and in cancer. (ed.ac.uk)
  • INTRODUCTION: Germ-line mutations of the APC gene are associated with familial adenomatous polyposis, and somatic mutations occur frequently in sporadic colorectal cancer. (duke.edu)
  • Double somatic SMARCB1 and NF2 mutations in sporadic spinal schwannoma. (cdc.gov)
  • These MLLT1 mutations were associated with changes in binding to H3K9ac, evidence of HOX and MYC (MYC-C) expression dysregulation, and were often accompanied by CTNNB1 mutations and evidence of Wnt pathway activation. (nature.com)
  • The discovery of germline mutations in the hepatocyte growth factor (HGF) receptor, Met, that predispose affected individuals to papillary renal cell carcinoma (HPRC) type 1, significantly strengthened mounting evidence of the oncogenic potential of this signaling pathway. (cancer.gov)
  • 17%) gemistocytic astrocytomas and in mutation with a sensitivity of 100% and 3 of 24 (13%) secondary glioblastomas. (who.int)
  • The development of drug-resistant secondary KIT mutations is a primary factor contributing to GIST recurrence following targeted therapy. (lu.se)
  • In summary, our data demonstrate that DDR1/2 contribute to KIT activation in GISTs and strengthen resistance to imatinib for both primary and secondary KIT mutants, providing a rationale for further exploration of DDR1/2 targeting in GIST treatment. (lu.se)
  • However, the possible oncogenic interactions between germline genetic risk variants and somatic mutations in triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (non-TNBC) have not been characterized. (hindawi.com)
  • An independent cohort of 98 BRCA mutation carriers was used for validation. (tau.ac.il)
  • CONCLUSIONS: We demonstrated that common germline variants are associated with EFS and OS among individuals with RMS. (bvsalud.org)
  • Breast cancer development and progression involve both germline and somatic mutations. (hindawi.com)
  • The scientists found that mutations began to occur at an accelerating rate during or soon after puberty, suggesting that aging begins in our teens. (neurosciencenews.com)
  • Even outside the hereditary cancer context, the presence of polymorphisms acting as genetic modifiers may contribute to a better or worse prognosis. (biomedcentral.com)
  • Multifocal nerve lesions and LZTR1 germline mutations in segmental schwannomatosis. (cdc.gov)
  • He has a particular interest in understanding how the interplay between inherited germline genetic factors and acquired somatic mutations contributes to disease. (vicc.org)
  • Our analysis reveals that the first cell division after fertilization produces ~3.4 mutations, followed by 2-3 mutations in subsequent generations. (nih.gov)
  • Cawthon said the DNA in our bodies is regularly damaged, and as we age our ability to fix these problems wanes and potentially harmful mutations collect. (newsweek.com)
  • Typically, various mechanisms repair this damage and prevent potentially harmful mutations, according to lead and corresponding author Richard Cawthon, M.D., Ph.D., a U of U Health research associate professor of human genetics. (neurosciencenews.com)
  • However, Cawthon and colleagues theorized that these mutations could be a biomarker for rates of aging and potentially predict lifespan in younger individuals as well as fertility in women. (neurosciencenews.com)
  • For example, if the first four children in a family have the mutation, the next child has the same 50% risk of inheriting the mutation. (wikipedia.org)
  • High-throughput genotyping and next-generation sequencing technologies have enabled discovery of genetic risk variants and acquired somatic mutations driving the disease. (hindawi.com)
  • ASD brains show an excess of somatic mutations in neural enhancer sequences compared with controls, suggesting that mosaic enhancer mutations may contribute to ASD risk. (nih.gov)
  • However, the researchers found no association between germline mutations and the risk of cancer. (newsweek.com)
  • Women harboring a germline mutation in the BRCA1 gene show a lifetime cumulative risk (LCR) between 44 and 68 % of developing breast cancer until 70 years of age. (biomedcentral.com)
  • One particular CHEK2 germline mutation, c.1100delC, has been shown to be associated with elevated breast cancer risk. (eur.nl)
  • Professor Joao Pedro de Magalhaes of the Institute of Ageing and Chronic Disease at the University of Liverpool who did not work on the paper told Newsweek: "this study fits the hypothesis that accumulation of DNA damage and mutations contributes to aging, although of course correlation does not imply causation, so it is not conclusive. (newsweek.com)
  • After adjusting for age, the researchers determined that individuals with the slowest rates of mutation accumulation were likely to live about five years longer than those who accumulated mutations more rapidly. (neurosciencenews.com)
  • Importantly, overactive NF-κB is frequently associated with B cell malignancy and, specifically, somatic gain-of-function CARD11 mutations are seen frequently in diffuse large B cell lymphoma (DLBCL). (wikipedia.org)
  • Co-author Dr. Richard Cawthon, University of Utah Health research associate and professor of human genetics, said: "Compared to a 32-year-old man with 75 mutations, we would expect a 40-year-old with the same number of mutations to be aging more slowly. (newsweek.com)
  • The families were part of the Centre d'Etude du Polymorphisme Humain (CEPH) consortium, which was central to many key investigations that have contributed toward a modern understanding of human genetics. (neurosciencenews.com)
  • Most mutations are localized within or just upstream of the coiled-coil domain (exons 4-9) of the protein. (wikipedia.org)
  • The BRCA1 185delAG allele is a common inherited mutation located close to the protein translation start site that is thought to produce a shortened, nonfunctional peptide. (jci.org)
  • Mutations in the BAP1 gene lead to production of an altered protein that cannot function normally and may be broken down prematurely. (medlineplus.gov)
  • Phenotypic analysis of these ' in locus ' mutations based on both expression of Kni protein and adult wing phenotypes, reveals novel unexpected features of L2-CRM function including evidence for a chromosome pairing-dependent process that promotes transcription. (elifesciences.org)
  • Mutations of this gene introduce a premature stop codon and result in truncated protein versions. (medscape.com)