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BRCA2 Biallelic Inactivation

MedGen UID:
1647774
•Concept ID:
C4684426
•
Cell or Molecular Dysfunction
Synonyms: BRCA2 Biallelic Gene Inactivation; BRCC2 Biallelic Gene Inactivation; Breast Cancer 2 Biallelic Gene Inactivation; Breast Cancer 2, Early Onset Biallelic Gene Inactivation; Breast Cancer Type 2 Susceptibility Biallelic Gene Inactivation; BROVCA2 Biallelic Gene Inactivation; FANCD1 Biallelic Gene Inactivation; XRCC11 Biallelic Gene Inactivation

Definition

The presence of mutations in both alleles of the BRCA2 gene that either lead to loss of expression of the BRCA2 protein or result in the translation of an inactive BRCA2 protein. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVBRCA2 Biallelic Inactivation

Professional guidelines

PubMed

The Impact of Li-Fraumeni and Germline Retinoblastoma Mutations on Leiomyosarcoma Initiation, Outcomes, and Genetic Testing Recommendations.
Dermawan JK, Abramson DH, Chiang S, Hensley ML, Tap WD, Movva S, Maki RG, Mandelker D, Antonescu CR
Clin Cancer Res 2024 Oct 15;30(20):4780-4790. doi: 10.1158/1078-0432.CCR-24-1160. PMID: 39150540Free PMC Article

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
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
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
Ovarian cancer genome.
Imyanitov EN
Methods Mol Biol 2013;1049:3-7. doi: 10.1007/978-1-62703-547-7_1. PMID: 23913204

Diagnosis

Pathogenic germline variants in non-BRCA1/2 homologous recombination genes in ovarian cancer: Analysis of tumor phenotype and survival.
Kahn RM, Selenica P, Boerner T, Roche KL, Xiao Y, Sia TY, Maio A, Kemel Y, Sheehan M, Salo-Mullen E, Breen KE, Zhou Q, Iasonos A, Grisham RN, O'Cearbhaill RE, Chi DS, Berger MF, Kundra R, Schultz N, Ellenson LH, Stadler ZK, Offit K, Mandelker D, Aghajanian C, Zamarin D, Sabbatini P, Weigelt B, Liu YL
Gynecol Oncol 2024 Jan;180:35-43. Epub 2023 Dec 1 doi: 10.1016/j.ygyno.2023.11.019. PMID: 38041901Free 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
Biallelic Inactivation of BRCA2 in Platinum-sensitive Metastatic Castration-resistant Prostate Cancer.
Cheng HH, Pritchard CC, Boyd T, Nelson PS, Montgomery B
Eur Urol 2016 Jun;69(6):992-5. Epub 2015 Dec 24 doi: 10.1016/j.eururo.2015.11.022. PMID: 26724258Free 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

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
Germline Pathogenic Variants Impact Clinicopathology of Advanced Lung Cancer.
Mukherjee S, Bandlamudi C, Hellmann MD, Kemel Y, Drill E, Rizvi H, Tkachuk K, Khurram A, Walsh MF, Zauderer MG, Mandelker D, Topka S, Zehir A, Srinivasan P, Esai Selvan M, Carlo MI, Cadoo KA, Latham A, Hamilton JG, Liu YL, Lipkin SM, Belhadj S, Bond GL, Gümüş ZH, Klein RJ, Ladanyi M, Solit DB, Robson ME, Jones DR, Kris MG, Vijai J, Stadler ZK, Amos CI, Taylor BS, Berger MF, Rudin CM, Offit K
Cancer Epidemiol Biomarkers Prev 2022 Jul 1;31(7):1450-1459. doi: 10.1158/1055-9965.EPI-21-1287. PMID: 35477182Free 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

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