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Inactivating BRCA1 Gene Mutation

MedGen UID:
267019
•Concept ID:
C1511023
•
Cell or Molecular Dysfunction
Synonyms: BRCA1 Gene Inactivation; BRCA1 Inactivation; BRCA1 Loss of Function Gene Mutation; BRCA1 Loss of Function Mutation; BRCA1 Tumor-Suppressor Gene Inactivation; Inactivating BRCA1 Mutation; Inactivating Breast Cancer 1 Gene Mutation; Inactivating Breast Cancer 1, Early Onset Gene Mutation; Inactivating Breast Cancer Type 1 Susceptibility Gene Mutation; Inactivating BROVCA1 Gene Mutation; Loss of Function BRCA1 Gene Mutation; Loss of Function BRCA1 Mutation

Definition

A mutation in the BRCA1 gene that either leads to loss of expression or results in the translation of an inactive breast cancer type 1 susceptibility protein. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVInactivating BRCA1 Gene Mutation

Professional guidelines

PubMed

CDH1 Genotype Exploration in Women With Hereditary Lobular Breast Cancer Phenotype.
Corso G, Marino E, Zanzottera C, Oliveira C, Bernard L, Macis D, Figueiredo J, Pereira J, Carneiro P, Massari G, Barberis M, De Scalzi AM, Taormina SV, Sajjadi E, Sangalli C, Gandini S, D'Ecclesiis O, Trovato CM, Rotili A, Pesapane F, Nicosia L, La Vecchia C, Galimberti V, Guerini-Rocco E, Bonanni B, Veronesi P
JAMA Netw Open 2024 Apr 1;7(4):e247862. doi: 10.1001/jamanetworkopen.2024.7862. PMID: 38652475Free PMC Article
Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer.
Van Baelen K, Geukens T, Maetens M, Tjan-Heijnen V, Lord CJ, Linn S, Bidard FC, Richard F, Yang WW, Steele RE, Pettitt SJ, Van Ongeval C, De Schepper M, Isnaldi E, Nevelsteen I, Smeets A, Punie K, Voorwerk L, Wildiers H, Floris G, Vincent-Salomon A, Derksen PWB, Neven P, Senkus E, Sawyer E, Kok M, Desmedt C
Ann Oncol 2022 Aug;33(8):769-785. Epub 2022 May 21 doi: 10.1016/j.annonc.2022.05.006. PMID: 35605746
Characterization, Detection, and Treatment Approaches for Homologous Recombination Deficiency in Cancer.
O'Kane GM, Connor AA, Gallinger S
Trends Mol Med 2017 Dec;23(12):1121-1137. Epub 2017 Nov 10 doi: 10.1016/j.molmed.2017.10.007. PMID: 29133135

Recent clinical studies

Etiology

Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer.
Van Baelen K, Geukens T, Maetens M, Tjan-Heijnen V, Lord CJ, Linn S, Bidard FC, Richard F, Yang WW, Steele RE, Pettitt SJ, Van Ongeval C, De Schepper M, Isnaldi E, Nevelsteen I, Smeets A, Punie K, Voorwerk L, Wildiers H, Floris G, Vincent-Salomon A, Derksen PWB, Neven P, Senkus E, Sawyer E, Kok M, Desmedt C
Ann Oncol 2022 Aug;33(8):769-785. Epub 2022 May 21 doi: 10.1016/j.annonc.2022.05.006. PMID: 35605746
Tumour lineage shapes BRCA-mediated phenotypes.
Jonsson P, Bandlamudi C, Cheng ML, Srinivasan P, Chavan SS, Friedman ND, Rosen EY, Richards AL, Bouvier N, Selcuklu SD, Bielski CM, Abida W, Mandelker D, Birsoy O, Zhang L, Zehir A, Donoghue MTA, Baselga J, Offit K, Scher HI, O'Reilly EM, Stadler ZK, Schultz N, Socci ND, Viale A, Ladanyi M, Robson ME, Hyman DM, Berger MF, Solit DB, Taylor BS
Nature 2019 Jul;571(7766):576-579. Epub 2019 Jul 10 doi: 10.1038/s41586-019-1382-1. PMID: 31292550Free PMC Article
Whole-genome characterization of chemoresistant ovarian cancer.
Patch AM, Christie EL, Etemadmoghadam D, Garsed DW, George J, Fereday S, Nones K, Cowin P, Alsop K, Bailey PJ, Kassahn KS, Newell F, Quinn MC, Kazakoff S, Quek K, Wilhelm-Benartzi C, Curry E, Leong HS; Australian Ovarian Cancer Study Group, Hamilton A, Mileshkin L, Au-Yeung G, Kennedy C, Hung J, Chiew YE, Harnett P, Friedlander M, Quinn M, Pyman J, Cordner S, O'Brien P, Leditschke J, Young G, Strachan K, Waring P, Azar W, Mitchell C, Traficante N, Hendley J, Thorne H, Shackleton M, Miller DK, Arnau GM, Tothill RW, Holloway TP, Semple T, Harliwong I, Nourse C, Nourbakhsh E, Manning S, Idrisoglu S, Bruxner TJ, Christ AN, Poudel B, Holmes O, Anderson M, Leonard C, Lonie A, Hall N, Wood S, Taylor DF, Xu Q, Fink JL, Waddell N, Drapkin R, Stronach E, Gabra H, Brown R, Jewell A, Nagaraj SH, Markham E, Wilson PJ, Ellul J, McNally O, Doyle MA, Vedururu R, Stewart C, Lengyel E, Pearson JV, Waddell N, deFazio A, Grimmond SM, Bowtell DD
Nature 2015 May 28;521(7553):489-94. doi: 10.1038/nature14410. PMID: 26017449
BRCA1 as target for breast cancer prevention and therapy.
Romagnolo AP, Romagnolo DF, Selmin OI
Anticancer Agents Med Chem 2015;15(1):4-14. doi: 10.2174/1871520614666141020153543. PMID: 25329591
A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS).
Lindor NM, Guidugli L, Wang X, Vallée MP, Monteiro AN, Tavtigian S, Goldgar DE, Couch FJ
Hum Mutat 2012 Jan;33(1):8-21. Epub 2011 Nov 3 doi: 10.1002/humu.21627. PMID: 21990134Free PMC Article

Diagnosis

BRCA2 Germline Mutations Identify Gastric Cancers Responsive to PARP Inhibitors.
Petrelli A, Rizzolio S, Pietrantonio F, Bellomo SE, Benelli M, De Cecco L, Romagnoli D, Berrino E, Orrù C, Ribisi S, Moya-Rull D, Migliore C, Conticelli D, Maina IM, Puliga E, Serra V, Pellegrino B, Llop-Guevara A, Musolino A, Siena S, Sartore-Bianchi A, Prisciandaro M, Morano F, Antista M, Fumagalli U, De Manzoni G, Degiuli M, Baiocchi GL, Amisano MF, Ferrero A, Marchiò C, Corso S, Giordano S
Cancer Res 2023 May 15;83(10):1699-1710. doi: 10.1158/0008-5472.CAN-22-2620. PMID: 37129948Free PMC Article
Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer.
Van Baelen K, Geukens T, Maetens M, Tjan-Heijnen V, Lord CJ, Linn S, Bidard FC, Richard F, Yang WW, Steele RE, Pettitt SJ, Van Ongeval C, De Schepper M, Isnaldi E, Nevelsteen I, Smeets A, Punie K, Voorwerk L, Wildiers H, Floris G, Vincent-Salomon A, Derksen PWB, Neven P, Senkus E, Sawyer E, Kok M, Desmedt C
Ann Oncol 2022 Aug;33(8):769-785. Epub 2022 May 21 doi: 10.1016/j.annonc.2022.05.006. PMID: 35605746
Tumour lineage shapes BRCA-mediated phenotypes.
Jonsson P, Bandlamudi C, Cheng ML, Srinivasan P, Chavan SS, Friedman ND, Rosen EY, Richards AL, Bouvier N, Selcuklu SD, Bielski CM, Abida W, Mandelker D, Birsoy O, Zhang L, Zehir A, Donoghue MTA, Baselga J, Offit K, Scher HI, O'Reilly EM, Stadler ZK, Schultz N, Socci ND, Viale A, Ladanyi M, Robson ME, Hyman DM, Berger MF, Solit DB, Taylor BS
Nature 2019 Jul;571(7766):576-579. Epub 2019 Jul 10 doi: 10.1038/s41586-019-1382-1. PMID: 31292550Free PMC Article
Whole-genome characterization of chemoresistant ovarian cancer.
Patch AM, Christie EL, Etemadmoghadam D, Garsed DW, George J, Fereday S, Nones K, Cowin P, Alsop K, Bailey PJ, Kassahn KS, Newell F, Quinn MC, Kazakoff S, Quek K, Wilhelm-Benartzi C, Curry E, Leong HS; Australian Ovarian Cancer Study Group, Hamilton A, Mileshkin L, Au-Yeung G, Kennedy C, Hung J, Chiew YE, Harnett P, Friedlander M, Quinn M, Pyman J, Cordner S, O'Brien P, Leditschke J, Young G, Strachan K, Waring P, Azar W, Mitchell C, Traficante N, Hendley J, Thorne H, Shackleton M, Miller DK, Arnau GM, Tothill RW, Holloway TP, Semple T, Harliwong I, Nourse C, Nourbakhsh E, Manning S, Idrisoglu S, Bruxner TJ, Christ AN, Poudel B, Holmes O, Anderson M, Leonard C, Lonie A, Hall N, Wood S, Taylor DF, Xu Q, Fink JL, Waddell N, Drapkin R, Stronach E, Gabra H, Brown R, Jewell A, Nagaraj SH, Markham E, Wilson PJ, Ellul J, McNally O, Doyle MA, Vedururu R, Stewart C, Lengyel E, Pearson JV, Waddell N, deFazio A, Grimmond SM, Bowtell DD
Nature 2015 May 28;521(7553):489-94. doi: 10.1038/nature14410. PMID: 26017449
A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS).
Lindor NM, Guidugli L, Wang X, Vallée MP, Monteiro AN, Tavtigian S, Goldgar DE, Couch FJ
Hum Mutat 2012 Jan;33(1):8-21. Epub 2011 Nov 3 doi: 10.1002/humu.21627. PMID: 21990134Free PMC Article

Therapy

BRCA2 Germline Mutations Identify Gastric Cancers Responsive to PARP Inhibitors.
Petrelli A, Rizzolio S, Pietrantonio F, Bellomo SE, Benelli M, De Cecco L, Romagnoli D, Berrino E, Orrù C, Ribisi S, Moya-Rull D, Migliore C, Conticelli D, Maina IM, Puliga E, Serra V, Pellegrino B, Llop-Guevara A, Musolino A, Siena S, Sartore-Bianchi A, Prisciandaro M, Morano F, Antista M, Fumagalli U, De Manzoni G, Degiuli M, Baiocchi GL, Amisano MF, Ferrero A, Marchiò C, Corso S, Giordano S
Cancer Res 2023 May 15;83(10):1699-1710. doi: 10.1158/0008-5472.CAN-22-2620. PMID: 37129948Free PMC Article
Targeting DNA damage response pathways in cancer.
Groelly FJ, Fawkes M, Dagg RA, Blackford AN, Tarsounas M
Nat Rev Cancer 2023 Feb;23(2):78-94. Epub 2022 Dec 5 doi: 10.1038/s41568-022-00535-5. PMID: 36471053
Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer.
Van Baelen K, Geukens T, Maetens M, Tjan-Heijnen V, Lord CJ, Linn S, Bidard FC, Richard F, Yang WW, Steele RE, Pettitt SJ, Van Ongeval C, De Schepper M, Isnaldi E, Nevelsteen I, Smeets A, Punie K, Voorwerk L, Wildiers H, Floris G, Vincent-Salomon A, Derksen PWB, Neven P, Senkus E, Sawyer E, Kok M, Desmedt C
Ann Oncol 2022 Aug;33(8):769-785. Epub 2022 May 21 doi: 10.1016/j.annonc.2022.05.006. PMID: 35605746
Tumour lineage shapes BRCA-mediated phenotypes.
Jonsson P, Bandlamudi C, Cheng ML, Srinivasan P, Chavan SS, Friedman ND, Rosen EY, Richards AL, Bouvier N, Selcuklu SD, Bielski CM, Abida W, Mandelker D, Birsoy O, Zhang L, Zehir A, Donoghue MTA, Baselga J, Offit K, Scher HI, O'Reilly EM, Stadler ZK, Schultz N, Socci ND, Viale A, Ladanyi M, Robson ME, Hyman DM, Berger MF, Solit DB, Taylor BS
Nature 2019 Jul;571(7766):576-579. Epub 2019 Jul 10 doi: 10.1038/s41586-019-1382-1. PMID: 31292550Free PMC Article
BRCA1 as target for breast cancer prevention and therapy.
Romagnolo AP, Romagnolo DF, Selmin OI
Anticancer Agents Med Chem 2015;15(1):4-14. doi: 10.2174/1871520614666141020153543. PMID: 25329591

Prognosis

Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer.
Van Baelen K, Geukens T, Maetens M, Tjan-Heijnen V, Lord CJ, Linn S, Bidard FC, Richard F, Yang WW, Steele RE, Pettitt SJ, Van Ongeval C, De Schepper M, Isnaldi E, Nevelsteen I, Smeets A, Punie K, Voorwerk L, Wildiers H, Floris G, Vincent-Salomon A, Derksen PWB, Neven P, Senkus E, Sawyer E, Kok M, Desmedt C
Ann Oncol 2022 Aug;33(8):769-785. Epub 2022 May 21 doi: 10.1016/j.annonc.2022.05.006. PMID: 35605746
Molecular tests for prediction of tumor sensitivity to cytotoxic drugs.
Imyanitov EN, Iyevleva AG
Cancer Lett 2022 Feb 1;526:41-52. Epub 2021 Nov 20 doi: 10.1016/j.canlet.2021.11.021. PMID: 34808283
The BRCA1/BARD1 ubiquitin ligase and its substrates.
Witus SR, Stewart MD, Klevit RE
Biochem J 2021 Sep 30;478(18):3467-3483. doi: 10.1042/BCJ20200864. PMID: 34591954Free PMC Article
Critical role for BRCA1 expression as a marker of chemosensitivity response and prognosis.
De Luca P, De Siervi A
Front Biosci (Elite Ed) 2016 Jan 1;8(1):72-83. doi: 10.2741/E752. PMID: 26709647
A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS).
Lindor NM, Guidugli L, Wang X, Vallée MP, Monteiro AN, Tavtigian S, Goldgar DE, Couch FJ
Hum Mutat 2012 Jan;33(1):8-21. Epub 2011 Nov 3 doi: 10.1002/humu.21627. PMID: 21990134Free PMC Article

Clinical prediction guides

Germline drivers of gynecologic carcinosarcomas.
Sia TY, Gordhandas SB, Birsoy O, Kemel Y, Maio A, Salo-Mullen E, Sheehan M, Hensley ML, Rubinstein M, Makker V, Grisham RN, O'Cearbhaill RE, Roche KL, Mueller JJ, Leitao MM Jr, Sonoda Y, Chi DS, Abu-Rustum NR, Berger MF, Ellenson LH, Latham A, Stadler Z, Offit K, Aghajanian C, Weigelt B, Mandelker D, Liu YL
Gynecol Oncol 2023 Jul;174:34-41. Epub 2023 May 5 doi: 10.1016/j.ygyno.2023.04.024. PMID: 37149903Free PMC Article
BRCA2 Germline Mutations Identify Gastric Cancers Responsive to PARP Inhibitors.
Petrelli A, Rizzolio S, Pietrantonio F, Bellomo SE, Benelli M, De Cecco L, Romagnoli D, Berrino E, Orrù C, Ribisi S, Moya-Rull D, Migliore C, Conticelli D, Maina IM, Puliga E, Serra V, Pellegrino B, Llop-Guevara A, Musolino A, Siena S, Sartore-Bianchi A, Prisciandaro M, Morano F, Antista M, Fumagalli U, De Manzoni G, Degiuli M, Baiocchi GL, Amisano MF, Ferrero A, Marchiò C, Corso S, Giordano S
Cancer Res 2023 May 15;83(10):1699-1710. doi: 10.1158/0008-5472.CAN-22-2620. PMID: 37129948Free PMC Article
Molecular tests for prediction of tumor sensitivity to cytotoxic drugs.
Imyanitov EN, Iyevleva AG
Cancer Lett 2022 Feb 1;526:41-52. Epub 2021 Nov 20 doi: 10.1016/j.canlet.2021.11.021. PMID: 34808283
Tumour lineage shapes BRCA-mediated phenotypes.
Jonsson P, Bandlamudi C, Cheng ML, Srinivasan P, Chavan SS, Friedman ND, Rosen EY, Richards AL, Bouvier N, Selcuklu SD, Bielski CM, Abida W, Mandelker D, Birsoy O, Zhang L, Zehir A, Donoghue MTA, Baselga J, Offit K, Scher HI, O'Reilly EM, Stadler ZK, Schultz N, Socci ND, Viale A, Ladanyi M, Robson ME, Hyman DM, Berger MF, Solit DB, Taylor BS
Nature 2019 Jul;571(7766):576-579. Epub 2019 Jul 10 doi: 10.1038/s41586-019-1382-1. PMID: 31292550Free PMC Article
Whole-genome characterization of chemoresistant ovarian cancer.
Patch AM, Christie EL, Etemadmoghadam D, Garsed DW, George J, Fereday S, Nones K, Cowin P, Alsop K, Bailey PJ, Kassahn KS, Newell F, Quinn MC, Kazakoff S, Quek K, Wilhelm-Benartzi C, Curry E, Leong HS; Australian Ovarian Cancer Study Group, Hamilton A, Mileshkin L, Au-Yeung G, Kennedy C, Hung J, Chiew YE, Harnett P, Friedlander M, Quinn M, Pyman J, Cordner S, O'Brien P, Leditschke J, Young G, Strachan K, Waring P, Azar W, Mitchell C, Traficante N, Hendley J, Thorne H, Shackleton M, Miller DK, Arnau GM, Tothill RW, Holloway TP, Semple T, Harliwong I, Nourse C, Nourbakhsh E, Manning S, Idrisoglu S, Bruxner TJ, Christ AN, Poudel B, Holmes O, Anderson M, Leonard C, Lonie A, Hall N, Wood S, Taylor DF, Xu Q, Fink JL, Waddell N, Drapkin R, Stronach E, Gabra H, Brown R, Jewell A, Nagaraj SH, Markham E, Wilson PJ, Ellul J, McNally O, Doyle MA, Vedururu R, Stewart C, Lengyel E, Pearson JV, Waddell N, deFazio A, Grimmond SM, Bowtell DD
Nature 2015 May 28;521(7553):489-94. doi: 10.1038/nature14410. PMID: 26017449

Recent systematic reviews

Different prognostic roles of tumor suppressor gene BAP1 in cancer: A systematic review with meta-analysis.
Luchini C, Veronese N, Yachida S, Cheng L, Nottegar A, Stubbs B, Solmi M, Capelli P, Pea A, Barbareschi M, Fassan M, Wood LD, Scarpa A
Genes Chromosomes Cancer 2016 Oct;55(10):741-9. Epub 2016 Jul 7 doi: 10.1002/gcc.22381. PMID: 27223342

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