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BRCA1 Biallelic Inactivation

MedGen UID:
1631450
•Concept ID:
C4684425
•
Cell or Molecular Dysfunction
Synonyms: BRCA1 Biallelic Gene Inactivation; Breast Cancer 1 Biallelic Gene Inactivation; Breast Cancer 1, Early Onset Biallelic Gene Inactivation; Breast Cancer Type 1 Susceptibility Biallelic Gene Inactivation; BROVCA1 Biallelic Gene Inactivation

Definition

The presence of mutations in both alleles of the BRCA1 gene that either lead to loss of expression of the BRCA1 protein or result in the translation of an inactive BRCA1 protein. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVBRCA1 Biallelic Inactivation

Professional guidelines

PubMed

Patients with Biallelic BRCA1/2 Inactivation Respond to Olaparib Treatment Across Histologic Tumor Types.
van der Wijngaart H, Hoes LR, van Berge Henegouwen JM, van der Velden DL, Zeverijn LJ, Roepman P, van Werkhoven E, de Leng WWJ, Jansen AML, Mehra N, Robbrecht DGJ, Labots M, de Groot DJA, Hoeben A, Hamberg P, Gelderblom H, Voest EE, Verheul HMW
Clin Cancer Res 2021 Nov 15;27(22):6106-6114. Epub 2021 Sep 2 doi: 10.1158/1078-0432.CCR-21-1104. PMID: 34475104

Recent clinical studies

Etiology

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
PBRM1, SETD2 and BAP1 - the trinity of 3p in clear cell renal cell carcinoma.
Walton J, Lawson K, Prinos P, Finelli A, Arrowsmith C, Ailles L
Nat Rev Urol 2023 Feb;20(2):96-115. Epub 2022 Oct 17 doi: 10.1038/s41585-022-00659-1. PMID: 36253570
Pan-cancer landscape of homologous recombination deficiency.
Nguyen L, W M Martens J, Van Hoeck A, Cuppen E
Nat Commun 2020 Nov 4;11(1):5584. doi: 10.1038/s41467-020-19406-4. PMID: 33149131Free PMC Article
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
Ovarian cancer genome.
Imyanitov EN
Methods Mol Biol 2013;1049:3-7. doi: 10.1007/978-1-62703-547-7_1. PMID: 23913204

Diagnosis

Recurrent Tumor Suppressor Alterations in Primary Pericardial Mesothelioma.
Schaefer IM, Mariño-Enríquez A, Hammer MM, Padera RF, Sholl LM
Mod Pathol 2023 Sep;36(9):100237. Epub 2023 Jun 8 doi: 10.1016/j.modpat.2023.100237. PMID: 37295554Free PMC Article
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
Pan-cancer landscape of homologous recombination deficiency.
Nguyen L, W M Martens J, Van Hoeck A, Cuppen E
Nat Commun 2020 Nov 4;11(1):5584. doi: 10.1038/s41467-020-19406-4. PMID: 33149131Free PMC Article
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
Ovarian cancer genome.
Imyanitov EN
Methods Mol Biol 2013;1049:3-7. doi: 10.1007/978-1-62703-547-7_1. PMID: 23913204

Therapy

Agnostic Administration of Targeted Anticancer Drugs: Looking for a Balance between Hype and Caution.
Aleksakhina SN, Ivantsov AO, Imyanitov EN
Int J Mol Sci 2024 Apr 7;25(7) doi: 10.3390/ijms25074094. PMID: 38612902Free PMC Article
Analysis of mutation status and homologous recombination deficiency in tumors of patients with germline BRCA1 or BRCA2 mutations and metastatic breast cancer: OlympiAD.
Hodgson D, Lai Z, Dearden S, Barrett JC, Harrington EA, Timms K, Lanchbury J, Wu W, Allen A, Senkus E, Domchek SM, Robson M
Ann Oncol 2021 Dec;32(12):1582-1589. Epub 2021 Sep 6 doi: 10.1016/j.annonc.2021.08.2154. PMID: 34500047
Genomic Features and Classification of Homologous Recombination Deficient Pancreatic Ductal Adenocarcinoma.
Golan T, O'Kane GM, Denroche RE, Raitses-Gurevich M, Grant RC, Holter S, Wang Y, Zhang A, Jang GH, Stossel C, Atias D, Halperin S, Berger R, Glick Y, Park JP, Cuggia A, Williamson L, Wong HL, Schaeffer DF, Renouf DJ, Borgida A, Dodd A, Wilson JM, Fischer SE, Notta F, Knox JJ, Zogopoulos G, Gallinger S
Gastroenterology 2021 May;160(6):2119-2132.e9. Epub 2021 Jan 30 doi: 10.1053/j.gastro.2021.01.220. PMID: 33524400
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
Biological and clinical evidence for somatic mutations in BRCA1 and BRCA2 as predictive markers for olaparib response in high-grade serous ovarian cancers in the maintenance setting.
Dougherty BA, Lai Z, Hodgson DR, Orr MCM, Hawryluk M, Sun J, Yelensky R, Spencer SK, Robertson JD, Ho TW, Fielding A, Ledermann JA, Barrett JC
Oncotarget 2017 Jul 4;8(27):43653-43661. doi: 10.18632/oncotarget.17613. PMID: 28525389Free PMC Article

Prognosis

Agnostic Administration of Targeted Anticancer Drugs: Looking for a Balance between Hype and Caution.
Aleksakhina SN, Ivantsov AO, Imyanitov EN
Int J Mol Sci 2024 Apr 7;25(7) doi: 10.3390/ijms25074094. PMID: 38612902Free PMC Article
Copy number alteration features in pan-cancer homologous recombination deficiency prediction and biology.
Yao H, Li H, Wang J, Wu T, Ning W, Diao K, Wu C, Wang G, Tao Z, Zhao X, Chen J, Sun X, Liu XS
Commun Biol 2023 May 16;6(1):527. doi: 10.1038/s42003-023-04901-3. PMID: 37193789Free PMC Article
Genomic Features and Classification of Homologous Recombination Deficient Pancreatic Ductal Adenocarcinoma.
Golan T, O'Kane GM, Denroche RE, Raitses-Gurevich M, Grant RC, Holter S, Wang Y, Zhang A, Jang GH, Stossel C, Atias D, Halperin S, Berger R, Glick Y, Park JP, Cuggia A, Williamson L, Wong HL, Schaeffer DF, Renouf DJ, Borgida A, Dodd A, Wilson JM, Fischer SE, Notta F, Knox JJ, Zogopoulos G, Gallinger S
Gastroenterology 2021 May;160(6):2119-2132.e9. Epub 2021 Jan 30 doi: 10.1053/j.gastro.2021.01.220. PMID: 33524400
Pan-cancer landscape of homologous recombination deficiency.
Nguyen L, W M Martens J, Van Hoeck A, Cuppen E
Nat Commun 2020 Nov 4;11(1):5584. doi: 10.1038/s41467-020-19406-4. PMID: 33149131Free PMC Article
Cancer Susceptibility Mutations in Patients With Urothelial Malignancies.
Carlo MI, Ravichandran V, Srinavasan P, Bandlamudi C, Kemel Y, Ceyhan-Birsoy O, Mukherjee S, Mandelker D, Chaim J, Knezevic A, Rana S, Fnu Z, Breen K, Arnold AG, Khurram A, Tkachuk K, Cipolla CK, Regazzi A, Hakimi AA, Al-Ahmadie H, Dalbagni G, Cadoo KA, Walsh MF, Teo MY, Funt SA, Coleman JA, Bochner BH, Iyer G, Solit DB, Stadler ZK, Zhang L, Rosenberg JE, Taylor BS, Robson ME, Berger MF, Vijai J, Bajorin DF, Offit K
J Clin Oncol 2020 Feb 10;38(5):406-414. Epub 2019 Dec 3 doi: 10.1200/JCO.19.01395. PMID: 31794323Free PMC Article

Clinical prediction guides

Recurrent Tumor Suppressor Alterations in Primary Pericardial Mesothelioma.
Schaefer IM, Mariño-Enríquez A, Hammer MM, Padera RF, Sholl LM
Mod Pathol 2023 Sep;36(9):100237. Epub 2023 Jun 8 doi: 10.1016/j.modpat.2023.100237. PMID: 37295554Free PMC Article
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
Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants.
Inagaki-Kawata Y, Yoshida K, Kawaguchi-Sakita N, Kawashima M, Nishimura T, Senda N, Shiozawa Y, Takeuchi Y, Inoue Y, Sato-Otsubo A, Fujii Y, Nannya Y, Suzuki E, Takada M, Tanaka H, Shiraishi Y, Chiba K, Kataoka Y, Torii M, Yoshibayashi H, Yamagami K, Okamura R, Moriguchi Y, Kato H, Tsuyuki S, Yamauchi A, Suwa H, Inamoto T, Miyano S, Ogawa S, Toi M
Commun Biol 2020 Oct 16;3(1):578. doi: 10.1038/s42003-020-01301-9. PMID: 33067557Free PMC Article
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
Molecular analysis of PALB2-associated breast cancers.
Lee JEA, Li N, Rowley SM, Cheasley D, Zethoven M, McInerny S, Gorringe KL, James PA, Campbell IG
J Pathol 2018 May;245(1):53-60. Epub 2018 Mar 30 doi: 10.1002/path.5055. PMID: 29431189

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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