BACKGROUND: Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 confer substantial increased lifetime risk for breast cancer, and in the case of BRCA1, for ovarian carcinoma as well. These two genes alone account for the vast majority of hereditary breast cancer families. Numerous mutations have been described in each gene, the majority of which are small insertions or deletions resulting in expression of a truncated protein. MATERIALS AND METHODS: Several common mutations can be detected using a polymerase chain reaction-mediated, site-directed mutagenesis assay, which transforms the amplicon derived from either the wild-type or mutant allele by adding or removing a restriction endonuclease site. We screened 49 putative sporadic breast tumors using this methodology, targeting four BRCA1 mutations (185delAG, 5382insC, R1443X, and E1250X) and a single BRCA2 mutation (6174delT). RESULTS: Using the polymerase chain reaction-mediated, site-directed mutagenesis assay, we identified two mutations, namely, a 185delAG mutation (BRCA1) and a 6174delT mutation (BRCA2). Interestingly, these two mutations were found in the same sample. None of the remaining 48 breast tumors showed evidence of these mutations. Allele-specific oligonucleotide probes were then employed in conjunction with the Universal GeneComb Test Kit, which confirmed the presence of mutations. CONCLUSIONS: Our data suggest that the common germline BRCA1 and BRCA2 mutations are infrequently encountered in sporadic breast cancers. The one case with dual BRCA1 and BRCA2 mutations suggests that this tumor may be hereditary in origin, despite the lack of a positive family history. Double heterozygosity for mutations in BRCA1 and BRCA2 may have increasingly significant implications with regard to predisposition to breast cancer.
BACKGROUND: Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 confer substantial increased lifetime risk for breast cancer, and in the case of BRCA1, for ovarian carcinoma as well. These two genes alone account for the vast majority of hereditary breast cancer families. Numerous mutations have been described in each gene, the majority of which are small insertions or deletions resulting in expression of a truncated protein. MATERIALS AND METHODS: Several common mutations can be detected using a polymerase chain reaction-mediated, site-directed mutagenesis assay, which transforms the amplicon derived from either the wild-type or mutant allele by adding or removing a restriction endonuclease site. We screened 49 putative sporadic breast tumors using this methodology, targeting four BRCA1 mutations (185delAG, 5382insC, R1443X, and E1250X) and a single BRCA2 mutation (6174delT). RESULTS: Using the polymerase chain reaction-mediated, site-directed mutagenesis assay, we identified two mutations, namely, a 185delAG mutation (BRCA1) and a 6174delT mutation (BRCA2). Interestingly, these two mutations were found in the same sample. None of the remaining 48 breast tumors showed evidence of these mutations. Allele-specific oligonucleotide probes were then employed in conjunction with the Universal GeneComb Test Kit, which confirmed the presence of mutations. CONCLUSIONS: Our data suggest that the common germline BRCA1 and BRCA2 mutations are infrequently encountered in sporadic breast cancers. The one case with dual BRCA1 and BRCA2 mutations suggests that this tumor may be hereditary in origin, despite the lack of a positive family history. Double heterozygosity for mutations in BRCA1 and BRCA2 may have increasingly significant implications with regard to predisposition to breast cancer.
Authors: Timothy R Rebbeck; Tara M Friebel; Nandita Mitra; Fei Wan; Stephanie Chen; Irene L Andrulis; Paraskevi Apostolou; Norbert Arnold; Banu K Arun; Daniel Barrowdale; Javier Benitez; Raanan Berger; Pascaline Berthet; Ake Borg; Saundra S Buys; Trinidad Caldes; Jonathan Carter; Jocelyne Chiquette; Kathleen B M Claes; Fergus J Couch; Cezary Cybulski; Mary B Daly; Miguel de la Hoya; Orland Diez; Susan M Domchek; Katherine L Nathanson; Katarzyna Durda; Steve Ellis; D Gareth Evans; Lenka Foretova; Eitan Friedman; Debra Frost; Patricia A Ganz; Judy Garber; Gord Glendon; Andrew K Godwin; Mark H Greene; Jacek Gronwald; Eric Hahnen; Emily Hallberg; Ute Hamann; Thomas V O Hansen; Evgeny N Imyanitov; Claudine Isaacs; Anna Jakubowska; Ramunas Janavicius; Katarzyna Jaworska-Bieniek; Esther M John; Beth Y Karlan; Bella Kaufman; KConFab Investigators; Ava Kwong; Yael Laitman; Christine Lasset; Conxi Lazaro; Jenny Lester; Niklas Loman; Jan Lubinski; Siranoush Manoukian; Gillian Mitchell; Marco Montagna; Susan L Neuhausen; Heli Nevanlinna; Dieter Niederacher; Robert L Nussbaum; Kenneth Offit; Edith Olah; Olufunmilayo I Olopade; Sue Kyung Park; Marion Piedmonte; Paolo Radice; Christine Rappaport-Fuerhauser; Matti A Rookus; Caroline Seynaeve; Jacques Simard; Christian F Singer; Penny Soucy; Melissa Southey; Dominique Stoppa-Lyonnet; Grzegorz Sukiennicki; Csilla I Szabo; Mariella Tancredi; Manuel R Teixeira; Soo-Hwang Teo; Mary Beth Terry; Mads Thomassen; Laima Tihomirova; Marc Tischkowitz; Amanda Ewart Toland; Aleksandra Toloczko-Grabarek; Nadine Tung; Elizabeth J van Rensburg; Danylo Villano; Shan Wang-Gohrke; Barbara Wappenschmidt; Jeffrey N Weitzel; Jamal Zidan; Kristin K Zorn; Lesley McGuffog; Douglas Easton; Georgia Chenevix-Trench; Antonis C Antoniou; Susan J Ramus Journal: Breast Cancer Res Date: 2016-11-11 Impact factor: 6.466
Authors: Jeremy Setton; Pier Selenica; Semanti Mukherjee; Rachna Shah; Isabella Pecorari; Biko McMillan; Isaac X Pei; Yelena Kemel; Ozge Ceyhan-Birsoy; Margaret Sheehan; Kaitlyn Tkachuk; David N Brown; Liying Zhang; Karen Cadoo; Simon Powell; Britta Weigelt; Mark Robson; Nadeem Riaz; Kenneth Offit; Jorge S Reis-Filho; Diana Mandelker Journal: NPJ Breast Cancer Date: 2021-10-11