scholarly journals BRCA1 and BRCA2 pathogenic sequence variants in women of African origin or ancestry

2019 ◽  
Vol 40 (10) ◽  
pp. 1781-1796 ◽  
Author(s):  
Tara M. Friebel ◽  
Irene L. Andrulis ◽  
Judith Balmaña ◽  
Amie M. Blanco ◽  
Fergus J. Couch ◽  
...  
Keyword(s):  
Sequence Variants ◽  
African Origin ◽  
Brca1 And Brca2

scholarly journals Detection of splicing aberrations caused by BRCA1 and BRCA2 sequence variants encoding missense substitutions: implications for prediction of pathogenicity

2010 ◽  
Vol 31 (6) ◽  
pp. E1484-E1505 ◽  
Author(s):  
Logan C. Walker ◽  
Phillip J. Whiley ◽  
Fergus J. Couch ◽  
Daniel J. Farrugia ◽  
Sue Healey ◽  
...  
Keyword(s):  
Sequence Variants ◽  
Brca1 And Brca2

scholarly journals The spectrum of BRCA1 and BRCA2 pathogenic sequence variants in Middle Eastern, North African, and South European countries

2019 ◽  
Vol 40 (11) ◽  
Author(s):  
Yael Laitman ◽  
Tara M. Friebel ◽  
Drakoulis Yannoukakos ◽  
Florentia Fostira ◽  
Irene Konstantopoulou ◽  
...  
Keyword(s):  
Middle Eastern ◽  
European Countries ◽  
Sequence Variants ◽  
North African ◽  
Brca1 And Brca2

scholarly journals Integrated Evaluation of DNA Sequence Variants of Unknown Clinical Significance: Application to BRCA1 and BRCA2

2004 ◽  
Vol 75 (4) ◽  
pp. 535-544 ◽  
Author(s):  
David E. Goldgar ◽  
Douglas F. Easton ◽  
Amie M. Deffenbaugh ◽  
Alvaro N.A. Monteiro ◽  
Sean V. Tavtigian ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Dna Sequence ◽  
Sequence Variants ◽  
Brca1 And Brca2 ◽  
Dna Sequence Variants

scholarly journals Identifying sequence variants contributing to hereditary breast and ovarian cancer in BRCA1 and BRCA2 negative breast and ovarian cancer patients

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Elisabeth Jarhelle ◽  
Hilde Monica Frostad Riise Stensland ◽  
Geir Åsmund Myge Hansen ◽  
Siri Skarsfjord ◽  
Christoffer Jonsrud ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ovarian Cancer ◽  
Cancer Patients ◽  
Genetic Risk ◽  
Genetic Risk Factors ◽  
Sequence Variants ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Pathogenic Variants

AbstractFamilies with breast and ovarian cancer are often tested for disease associated sequence variants in BRCA1 and BRCA2. Pathogenic sequence variants (PVs) in these two genes are known to increase breast and ovarian cancer risks in females. However, in most families no PVs are detected in these two genes. Currently, several studies have identified other genes involved in hereditary breast and ovarian cancer (HBOC). To identify genetic risk factors for breast and ovarian cancer in a Norwegian HBOC cohort, 101 breast and/or ovarian cancer patients negative for PVs and variants of unknown clinical significance (VUS) in BRCA1/2 were screened for PVs in 94 genes using next-generation sequencing. Sixteen genes were closely scrutinized. Nine different deleterious germline PVs/likely pathogenic variants (LPVs) were identified in seven genes in 12 patients: three in ATM, and one in CHEK2, ERCC5, FANCM, RAD51C, TP53 and WRN. Additionally, 32 different VUSs were identified and these require further characterization. For carriers of PV/LPV in many of these genes, there are no national clinical management programs in Norway. The diversity of genetic risk factors possibly involved in cancer development show the necessity for more knowledge to improve the clinical follow-up of this genetically diverse patient group.

71: The Breast Cancer Genes IARC Database: a tool to improve evaluation of BRCA1 and BRCA2 uncertain sequence variants

2010 ◽  
Vol 97 (1) ◽  
pp. S61
Author(s):  
Vallée Maxime ◽  
Fabienne Lesueur ◽  
Amanda Spurdle ◽  
Frans Hogervorst ◽  
David E Goldgar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sequence Variants ◽  
Cancer Genes ◽  
Brca1 And Brca2 ◽  
Breast Cancer Genes

scholarly journals Clinical Classification of BRCA1 and BRCA2 DNA Sequence Variants: The Value of Cytokeratin Profiles and Evolutionary Analysis—A Report From the kConFab Investigators

2008 ◽  
Vol 26 (10) ◽  
pp. 1657-1663 ◽  
Author(s):  
Amanda B. Spurdle ◽  
Sunil R. Lakhani ◽  
Sue Healey ◽  
Suzanne Parry ◽  
Leonard M. Da Silva ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Genetic Counseling ◽  
Amino Acid ◽  
Prior Probability ◽  
Evolutionary Conservation ◽  
Sequence Variants ◽  
Variant Classification ◽  
Brca1 And Brca2 ◽  
Cytokeratin 5 ◽  
Cytokeratin 14

Purpose Rare missense substitutions and in-frame deletions of BRCA1 and BRCA2 genes present a challenge for genetic counseling of individuals carrying such unclassified variants. We assessed the value of tumor immunohistochemical markers in conjunction with genetic and evolutionary approaches for investigating the clinical significance of unclassified variants. Patients and Methods We studied 10 BRCA1 and 12 BRCA2 variants identified in Australian families with breast cancer. Analyses assumed a prior probability based on revised cross-species sequence alignment methods assessing amino acid evolutionary conservation and position, combined with likelihoods from data on co-occurrence with pathogenic mutations in the same gene, segregation analysis, and immunohistochemistry. We specifically explored the value of estrogen receptor, cytokeratin 5/6, and cytokeratin 14 as tumor markers of BRCA1 mutation status. Results Posterior probabilities classified 72% of variants. BRCA1 variants IVS18+1 G>T (del exon 18) and 5632 T >A (V1838E) were classified as pathogenic, with >99% posterior probability of being deleterious, and tumor histopathology was particularly important for their classification. BRCA2 variant classification was improved over previous studies, largely by incorporating the prior probability of pathogenicity based on amino acid cross-species sequence alignments. Conclusion Variant classification was considerably improved by analysis of estrogen receptor, cytokeratin 5/6, and cytokeratin 14 tumor expression, and use of updated methods estimating the clinical relevance of amino acid evolutionary conservation and position. These methodologies may assist genetic counseling of individuals with unclassified sequence variants.

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