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Deleterious BRCA Gene Mutation

MedGen UID:
1647878
•Concept ID:
C4683642
•
Cell or Molecular Dysfunction
Synonyms: Deleterious BRCA Family Mutation; Deleterious BRCA Gene Family Mutation; Deleterious BRCA Mutation

Definition

A change in the nucleotide sequence of a gene in the BRCA family that is associated with increased risk of disease. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDeleterious BRCA Gene Mutation

Professional guidelines

PubMed

An Overview of PARP Inhibitors for the Treatment of Breast Cancer.
Cortesi L, Rugo HS, Jackisch C
Target Oncol 2021 May;16(3):255-282. Epub 2021 Mar 12 doi: 10.1007/s11523-021-00796-4. PMID: 33710534Free PMC Article
Current and future role of genetic screening in gynecologic malignancies.
Ring KL, Garcia C, Thomas MH, Modesitt SC
Am J Obstet Gynecol 2017 Nov;217(5):512-521. Epub 2017 Apr 12 doi: 10.1016/j.ajog.2017.04.011. PMID: 28411145
Genetic testing today.
Euhus D
Ann Surg Oncol 2014 Oct;21(10):3209-15. Epub 2014 Jul 17 doi: 10.1245/s10434-014-3906-0. PMID: 25029991

Recent clinical studies

Etiology

Detection of BRCA1, BRCA2, and ATM Alterations in Matched Tumor Tissue and Circulating Tumor DNA in Patients with Prostate Cancer Screened in PROfound.
Chi KN, Barnicle A, Sibilla C, Lai Z, Corcoran C, Barrett JC, Adelman CA, Qiu P, Easter A, Dearden S, Oxnard GR, Agarwal N, Azad A, de Bono J, Mateo J, Olmos D, Thiery-Vuillemin A, Harrington EA
Clin Cancer Res 2023 Jan 4;29(1):81-91. doi: 10.1158/1078-0432.CCR-22-0931. PMID: 36043882Free PMC Article
Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration.
Abida W, Patnaik A, Campbell D, Shapiro J, Bryce AH, McDermott R, Sautois B, Vogelzang NJ, Bambury RM, Voog E, Zhang J, Piulats JM, Ryan CJ, Merseburger AS, Daugaard G, Heidenreich A, Fizazi K, Higano CS, Krieger LE, Sternberg CN, Watkins SP, Despain D, Simmons AD, Loehr A, Dowson M, Golsorkhi T, Chowdhury S; TRITON2 investigators
J Clin Oncol 2020 Nov 10;38(32):3763-3772. Epub 2020 Aug 14 doi: 10.1200/JCO.20.01035. PMID: 32795228Free PMC Article
BRCA mutations and reproduction.
Daum H, Peretz T, Laufer N
Fertil Steril 2018 Jan;109(1):33-38. doi: 10.1016/j.fertnstert.2017.12.004. PMID: 29307397
Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial.
Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators
Lancet 2017 Oct 28;390(10106):1949-1961. Epub 2017 Sep 12 doi: 10.1016/S0140-6736(17)32440-6. PMID: 28916367Free PMC Article
A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes.
Easton DF, Deffenbaugh AM, Pruss D, Frye C, Wenstrup RJ, Allen-Brady K, Tavtigian SV, Monteiro AN, Iversen ES, Couch FJ, Goldgar DE
Am J Hum Genet 2007 Nov;81(5):873-83. Epub 2007 Sep 6 doi: 10.1086/521032. PMID: 17924331Free PMC Article

Diagnosis

Homologous Recombination Repair Gene Mutations to Predict Olaparib Plus Bevacizumab Efficacy in the First-Line Ovarian Cancer PAOLA-1/ENGOT-ov25 Trial.
Pujade-Lauraine E, Brown J, Barnicle A, Wessen J, Lao-Sirieix P, Criscione SW, du Bois A, Lorusso D, Romero I, Petru E, Yoshida H, Vergote I, Colombo N, Hietanen S, Provansal M, Schmalfeldt B, Pignata S, Martín Lorente C, Berton D, Runnebaum IB, Ray-Coquard I
JCO Precis Oncol 2023 Jan;7:e2200258. doi: 10.1200/PO.22.00258. PMID: 36716415Free PMC Article
Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration.
Abida W, Patnaik A, Campbell D, Shapiro J, Bryce AH, McDermott R, Sautois B, Vogelzang NJ, Bambury RM, Voog E, Zhang J, Piulats JM, Ryan CJ, Merseburger AS, Daugaard G, Heidenreich A, Fizazi K, Higano CS, Krieger LE, Sternberg CN, Watkins SP, Despain D, Simmons AD, Loehr A, Dowson M, Golsorkhi T, Chowdhury S; TRITON2 investigators
J Clin Oncol 2020 Nov 10;38(32):3763-3772. Epub 2020 Aug 14 doi: 10.1200/JCO.20.01035. PMID: 32795228Free PMC Article
BRCA mutations and reproduction.
Daum H, Peretz T, Laufer N
Fertil Steril 2018 Jan;109(1):33-38. doi: 10.1016/j.fertnstert.2017.12.004. PMID: 29307397
Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial.
Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators
Lancet 2017 Oct 28;390(10106):1949-1961. Epub 2017 Sep 12 doi: 10.1016/S0140-6736(17)32440-6. PMID: 28916367Free PMC Article
Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial.
Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott CL, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Dougherty B, Orr M, Hodgson D, Barrett JC, Matulonis U
Lancet Oncol 2014 Jul;15(8):852-61. Epub 2014 May 31 doi: 10.1016/S1470-2045(14)70228-1. PMID: 24882434

Therapy

Homologous Recombination Repair Gene Mutations to Predict Olaparib Plus Bevacizumab Efficacy in the First-Line Ovarian Cancer PAOLA-1/ENGOT-ov25 Trial.
Pujade-Lauraine E, Brown J, Barnicle A, Wessen J, Lao-Sirieix P, Criscione SW, du Bois A, Lorusso D, Romero I, Petru E, Yoshida H, Vergote I, Colombo N, Hietanen S, Provansal M, Schmalfeldt B, Pignata S, Martín Lorente C, Berton D, Runnebaum IB, Ray-Coquard I
JCO Precis Oncol 2023 Jan;7:e2200258. doi: 10.1200/PO.22.00258. PMID: 36716415Free PMC Article
Biomarkers Associating with PARP Inhibitor Benefit in Prostate Cancer in the TOPARP-B Trial.
Carreira S, Porta N, Arce-Gallego S, Seed G, Llop-Guevara A, Bianchini D, Rescigno P, Paschalis A, Bertan C, Baker C, Goodall J, Miranda S, Riisnaes R, Figueiredo I, Ferreira A, Pereira R, Crespo M, Gurel B, Nava Rodrigues D, Pettitt SJ, Yuan W, Serra V, Rekowski J, Lord CJ, Hall E, Mateo J, de Bono JS
Cancer Discov 2021 Nov;11(11):2812-2827. Epub 2021 May 27 doi: 10.1158/2159-8290.CD-21-0007. PMID: 34045297Free PMC Article
An Overview of PARP Inhibitors for the Treatment of Breast Cancer.
Cortesi L, Rugo HS, Jackisch C
Target Oncol 2021 May;16(3):255-282. Epub 2021 Mar 12 doi: 10.1007/s11523-021-00796-4. PMID: 33710534Free PMC Article
Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration.
Abida W, Patnaik A, Campbell D, Shapiro J, Bryce AH, McDermott R, Sautois B, Vogelzang NJ, Bambury RM, Voog E, Zhang J, Piulats JM, Ryan CJ, Merseburger AS, Daugaard G, Heidenreich A, Fizazi K, Higano CS, Krieger LE, Sternberg CN, Watkins SP, Despain D, Simmons AD, Loehr A, Dowson M, Golsorkhi T, Chowdhury S; TRITON2 investigators
J Clin Oncol 2020 Nov 10;38(32):3763-3772. Epub 2020 Aug 14 doi: 10.1200/JCO.20.01035. PMID: 32795228Free PMC Article
Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial.
Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators
Lancet 2017 Oct 28;390(10106):1949-1961. Epub 2017 Sep 12 doi: 10.1016/S0140-6736(17)32440-6. PMID: 28916367Free PMC Article

Prognosis

Homologous Recombination Repair Gene Mutations to Predict Olaparib Plus Bevacizumab Efficacy in the First-Line Ovarian Cancer PAOLA-1/ENGOT-ov25 Trial.
Pujade-Lauraine E, Brown J, Barnicle A, Wessen J, Lao-Sirieix P, Criscione SW, du Bois A, Lorusso D, Romero I, Petru E, Yoshida H, Vergote I, Colombo N, Hietanen S, Provansal M, Schmalfeldt B, Pignata S, Martín Lorente C, Berton D, Runnebaum IB, Ray-Coquard I
JCO Precis Oncol 2023 Jan;7:e2200258. doi: 10.1200/PO.22.00258. PMID: 36716415Free PMC Article
Biomarkers Associating with PARP Inhibitor Benefit in Prostate Cancer in the TOPARP-B Trial.
Carreira S, Porta N, Arce-Gallego S, Seed G, Llop-Guevara A, Bianchini D, Rescigno P, Paschalis A, Bertan C, Baker C, Goodall J, Miranda S, Riisnaes R, Figueiredo I, Ferreira A, Pereira R, Crespo M, Gurel B, Nava Rodrigues D, Pettitt SJ, Yuan W, Serra V, Rekowski J, Lord CJ, Hall E, Mateo J, de Bono JS
Cancer Discov 2021 Nov;11(11):2812-2827. Epub 2021 May 27 doi: 10.1158/2159-8290.CD-21-0007. PMID: 34045297Free PMC Article
Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial.
Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators
Lancet 2017 Oct 28;390(10106):1949-1961. Epub 2017 Sep 12 doi: 10.1016/S0140-6736(17)32440-6. PMID: 28916367Free PMC Article
Genetic testing today.
Euhus D
Ann Surg Oncol 2014 Oct;21(10):3209-15. Epub 2014 Jul 17 doi: 10.1245/s10434-014-3906-0. PMID: 25029991
A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes.
Easton DF, Deffenbaugh AM, Pruss D, Frye C, Wenstrup RJ, Allen-Brady K, Tavtigian SV, Monteiro AN, Iversen ES, Couch FJ, Goldgar DE
Am J Hum Genet 2007 Nov;81(5):873-83. Epub 2007 Sep 6 doi: 10.1086/521032. PMID: 17924331Free PMC Article

Clinical prediction guides

Olaparib and Ceralasertib (AZD6738) in Patients with Triple-Negative Advanced Breast Cancer: Results from Cohort E of the plasmaMATCH Trial (CRUK/15/010).
Ring A, Kilburn LS, Pearson A, Moretti L, Afshari-Mehr A, Wardley AM, Gurel B, Macpherson IR, Riisnaes R, Baird RD, Martin S, Roylance R, Johnson H, Ferreira A, Winter MC, Dunne K, Copson E, Hickish T, Burcombe R, Randle K, Serra V, Llop-Guevara A, Bliss JM, Turner NC
Clin Cancer Res 2023 Dec 1;29(23):4751-4759. doi: 10.1158/1078-0432.CCR-23-1696. PMID: 37773077Free PMC Article
Homologous Recombination Repair Gene Mutations to Predict Olaparib Plus Bevacizumab Efficacy in the First-Line Ovarian Cancer PAOLA-1/ENGOT-ov25 Trial.
Pujade-Lauraine E, Brown J, Barnicle A, Wessen J, Lao-Sirieix P, Criscione SW, du Bois A, Lorusso D, Romero I, Petru E, Yoshida H, Vergote I, Colombo N, Hietanen S, Provansal M, Schmalfeldt B, Pignata S, Martín Lorente C, Berton D, Runnebaum IB, Ray-Coquard I
JCO Precis Oncol 2023 Jan;7:e2200258. doi: 10.1200/PO.22.00258. PMID: 36716415Free PMC Article
Biomarkers Associating with PARP Inhibitor Benefit in Prostate Cancer in the TOPARP-B Trial.
Carreira S, Porta N, Arce-Gallego S, Seed G, Llop-Guevara A, Bianchini D, Rescigno P, Paschalis A, Bertan C, Baker C, Goodall J, Miranda S, Riisnaes R, Figueiredo I, Ferreira A, Pereira R, Crespo M, Gurel B, Nava Rodrigues D, Pettitt SJ, Yuan W, Serra V, Rekowski J, Lord CJ, Hall E, Mateo J, de Bono JS
Cancer Discov 2021 Nov;11(11):2812-2827. Epub 2021 May 27 doi: 10.1158/2159-8290.CD-21-0007. PMID: 34045297Free PMC Article
Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration.
Abida W, Patnaik A, Campbell D, Shapiro J, Bryce AH, McDermott R, Sautois B, Vogelzang NJ, Bambury RM, Voog E, Zhang J, Piulats JM, Ryan CJ, Merseburger AS, Daugaard G, Heidenreich A, Fizazi K, Higano CS, Krieger LE, Sternberg CN, Watkins SP, Despain D, Simmons AD, Loehr A, Dowson M, Golsorkhi T, Chowdhury S; TRITON2 investigators
J Clin Oncol 2020 Nov 10;38(32):3763-3772. Epub 2020 Aug 14 doi: 10.1200/JCO.20.01035. PMID: 32795228Free PMC Article
A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes.
Easton DF, Deffenbaugh AM, Pruss D, Frye C, Wenstrup RJ, Allen-Brady K, Tavtigian SV, Monteiro AN, Iversen ES, Couch FJ, Goldgar DE
Am J Hum Genet 2007 Nov;81(5):873-83. Epub 2007 Sep 6 doi: 10.1086/521032. PMID: 17924331Free PMC Article

Recent systematic reviews

Physical Activity in Young BRCA Carriers and Reduced Risk of Breast Cancer.
Bucy AM, Valencia CI, Howe CL, Larkin TJ, Conard KD, Anderlik EW, Valdivi SI, Bea JW
Am J Prev Med 2022 Nov;63(5):837-845. Epub 2022 Jun 20 doi: 10.1016/j.amepre.2022.04.022. PMID: 35738959Free PMC Article
BRCA1/2 germline missense mutations: a systematic review.
Corso G, Feroce I, Intra M, Toesca A, Magnoni F, Sargenti M, Naninato P, Caldarella P, Pagani G, Vento A, Veronesi P, Bonanni B, Galimberti V
Eur J Cancer Prev 2018 May;27(3):279-286. doi: 10.1097/CEJ.0000000000000337. PMID: 28277317

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