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Deficiency of homologous recombination deoxyribonucleic acid repair

MedGen UID:
889474
•Concept ID:
C4049599
•
Cell or Molecular Dysfunction
Synonyms: Deficiency of homologous recombination DNA (deoxyribonucleic acid) repair; Deficiency of homologous recombination repair; Homologous Recombination Deficiency; Homologous Recombination Repair Deficiency; HRR Deficiency
SNOMED CT: Deficiency of homologous recombination repair (1255472001); Deficiency of homologous recombination deoxyribonucleic acid repair (1255472001); Deficiency of homologous recombination DNA (deoxyribonucleic acid) repair (1255472001)

Definition

A DNA repair abnormality caused by mutations in one or more genes that are involved in homologous recombination repair. Deficient homologous recombination is associated with numerous neoplastic diseases and developmental disorders related to chromosomal nondisjunction. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDeficiency of homologous recombination deoxyribonucleic acid repair

Professional guidelines

PubMed

Molecular Genetics of Prostate Cancer and Role of Genomic Testing.
Akhoundova D, Feng FY, Pritchard CC, Rubin MA
Surg Pathol Clin 2022 Dec;15(4):617-628. Epub 2022 Oct 13 doi: 10.1016/j.path.2022.08.002. PMID: 36344179
Homologous Recombination Deficiency: Cancer Predispositions and Treatment Implications.
Toh M, Ngeow J
Oncologist 2021 Sep;26(9):e1526-e1537. Epub 2021 Jun 2 doi: 10.1002/onco.13829. PMID: 34021944Free PMC Article
ESMO recommendations on predictive biomarker testing for homologous recombination deficiency and PARP inhibitor benefit in ovarian cancer.
Miller RE, Leary A, Scott CL, Serra V, Lord CJ, Bowtell D, Chang DK, Garsed DW, Jonkers J, Ledermann JA, Nik-Zainal S, Ray-Coquard I, Shah SP, Matias-Guiu X, Swisher EM, Yates LR
Ann Oncol 2020 Dec;31(12):1606-1622. Epub 2020 Sep 28 doi: 10.1016/j.annonc.2020.08.2102. PMID: 33004253

Recent clinical studies

Etiology

Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial.
Agarwal N, Azad AA, Carles J, Fay AP, Matsubara N, Heinrich D, Szczylik C, De Giorgi U, Young Joung J, Fong PCC, Voog E, Jones RJ, Shore ND, Dunshee C, Zschäbitz S, Oldenburg J, Lin X, Healy CG, Di Santo N, Zohren F, Fizazi K
Lancet 2023 Jul 22;402(10398):291-303. Epub 2023 Jun 4 doi: 10.1016/S0140-6736(23)01055-3. PMID: 37285865
The pancreatic cancer genome revisited.
Hayashi A, Hong J, Iacobuzio-Donahue CA
Nat Rev Gastroenterol Hepatol 2021 Jul;18(7):469-481. Epub 2021 Jun 4 doi: 10.1038/s41575-021-00463-z. PMID: 34089011
Homologous Recombination Deficiency: Cancer Predispositions and Treatment Implications.
Toh M, Ngeow J
Oncologist 2021 Sep;26(9):e1526-e1537. Epub 2021 Jun 2 doi: 10.1002/onco.13829. PMID: 34021944Free 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
Temozolomide: mechanisms of action, repair and resistance.
Zhang J, Stevens MF, Bradshaw TD
Curr Mol Pharmacol 2012 Jan;5(1):102-14. doi: 10.2174/1874467211205010102. PMID: 22122467

Diagnosis

Transcription-replication conflicts underlie sensitivity to PARP inhibitors.
Petropoulos M, Karamichali A, Rossetti GG, Freudenmann A, Iacovino LG, Dionellis VS, Sotiriou SK, Halazonetis TD
Nature 2024 Apr;628(8007):433-441. Epub 2024 Mar 20 doi: 10.1038/s41586-024-07217-2. PMID: 38509368Free PMC Article
Homologous Recombination Repair Deficiency: An Overview for Pathologists.
Doig KD, Fellowes AP, Fox SB
Mod Pathol 2023 Mar;36(3):100049. Epub 2023 Jan 10 doi: 10.1016/j.modpat.2022.100049. PMID: 36788098
Homologous Recombination Deficiencies and Hereditary Tumors.
Yamamoto H, Hirasawa A
Int J Mol Sci 2021 Dec 29;23(1) doi: 10.3390/ijms23010348. PMID: 35008774Free PMC Article
PARP inhibitor resistance: the underlying mechanisms and clinical implications.
Li H, Liu ZY, Wu N, Chen YC, Cheng Q, Wang J
Mol Cancer 2020 Jun 20;19(1):107. doi: 10.1186/s12943-020-01227-0. PMID: 32563252Free PMC Article
The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer.
Smith J, Tho LM, Xu N, Gillespie DA
Adv Cancer Res 2010;108:73-112. doi: 10.1016/B978-0-12-380888-2.00003-0. PMID: 21034966

Therapy

Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial.
Agarwal N, Azad AA, Carles J, Fay AP, Matsubara N, Heinrich D, Szczylik C, De Giorgi U, Young Joung J, Fong PCC, Voog E, Jones RJ, Shore ND, Dunshee C, Zschäbitz S, Oldenburg J, Lin X, Healy CG, Di Santo N, Zohren F, Fizazi K
Lancet 2023 Jul 22;402(10398):291-303. Epub 2023 Jun 4 doi: 10.1016/S0140-6736(23)01055-3. PMID: 37285865
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
Tackling PARP inhibitor resistance.
Fugger K, Hewitt G, West SC, Boulton SJ
Trends Cancer 2021 Dec;7(12):1102-1118. Epub 2021 Sep 22 doi: 10.1016/j.trecan.2021.08.007. PMID: 34563478
Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer.
Konstantinopoulos PA, Ceccaldi R, Shapiro GI, D'Andrea AD
Cancer Discov 2015 Nov;5(11):1137-54. Epub 2015 Oct 13 doi: 10.1158/2159-8290.CD-15-0714. PMID: 26463832Free PMC Article
Temozolomide: mechanisms of action, repair and resistance.
Zhang J, Stevens MF, Bradshaw TD
Curr Mol Pharmacol 2012 Jan;5(1):102-14. doi: 10.2174/1874467211205010102. PMID: 22122467

Prognosis

NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance.
Chen H, Li Y, Li H, Chen X, Fu H, Mao D, Chen W, Lan L, Wang C, Hu K, Li J, Zhu C, Evans I, Cheung E, Lu D, He Y, Behrens A, Yin D, Zhang C
Nature 2024 Jul;631(8021):663-669. Epub 2024 Jul 3 doi: 10.1038/s41586-024-07620-9. PMID: 38961290Free PMC Article
Homologous Recombination Repair Deficiency: An Overview for Pathologists.
Doig KD, Fellowes AP, Fox SB
Mod Pathol 2023 Mar;36(3):100049. Epub 2023 Jan 10 doi: 10.1016/j.modpat.2022.100049. PMID: 36788098
Molecular Genetics of Prostate Cancer and Role of Genomic Testing.
Akhoundova D, Feng FY, Pritchard CC, Rubin MA
Surg Pathol Clin 2022 Dec;15(4):617-628. Epub 2022 Oct 13 doi: 10.1016/j.path.2022.08.002. PMID: 36344179
Triple-negative breast cancer: promising prognostic biomarkers currently in development.
Sukumar J, Gast K, Quiroga D, Lustberg M, Williams N
Expert Rev Anticancer Ther 2021 Feb;21(2):135-148. doi: 10.1080/14737140.2021.1840984. PMID: 33198517Free 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

Clinical prediction guides

NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance.
Chen H, Li Y, Li H, Chen X, Fu H, Mao D, Chen W, Lan L, Wang C, Hu K, Li J, Zhu C, Evans I, Cheung E, Lu D, He Y, Behrens A, Yin D, Zhang C
Nature 2024 Jul;631(8021):663-669. Epub 2024 Jul 3 doi: 10.1038/s41586-024-07620-9. PMID: 38961290Free PMC Article
Homologous Recombination Repair Deficiency: An Overview for Pathologists.
Doig KD, Fellowes AP, Fox SB
Mod Pathol 2023 Mar;36(3):100049. Epub 2023 Jan 10 doi: 10.1016/j.modpat.2022.100049. PMID: 36788098
Molecular Genetics of Prostate Cancer and Role of Genomic Testing.
Akhoundova D, Feng FY, Pritchard CC, Rubin MA
Surg Pathol Clin 2022 Dec;15(4):617-628. Epub 2022 Oct 13 doi: 10.1016/j.path.2022.08.002. PMID: 36344179
A decade of clinical development of PARP inhibitors in perspective.
Mateo J, Lord CJ, Serra V, Tutt A, Balmaña J, Castroviejo-Bermejo M, Cruz C, Oaknin A, Kaye SB, de Bono JS
Ann Oncol 2019 Sep 1;30(9):1437-1447. doi: 10.1093/annonc/mdz192. PMID: 31218365Free PMC Article
Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas.
Knijnenburg TA, Wang L, Zimmermann MT, Chambwe N, Gao GF, Cherniack AD, Fan H, Shen H, Way GP, Greene CS, Liu Y, Akbani R, Feng B, Donehower LA, Miller C, Shen Y, Karimi M, Chen H, Kim P, Jia P, Shinbrot E, Zhang S, Liu J, Hu H, Bailey MH, Yau C, Wolf D, Zhao Z, Weinstein JN, Li L, Ding L, Mills GB, Laird PW, Wheeler DA, Shmulevich I; Cancer Genome Atlas Research Network, Monnat RJ Jr, Xiao Y, Wang C
Cell Rep 2018 Apr 3;23(1):239-254.e6. doi: 10.1016/j.celrep.2018.03.076. PMID: 29617664Free PMC Article

Recent systematic reviews

The efficacy and safety of PARP inhibitors in mCRPC with HRR mutation in second-line treatment: a systematic review and bayesian network meta-analysis.
Zhu Q, Chen J, Liu H, Zhao J, Xu C, Sun G, Zeng H
BMC Cancer 2024 Jun 8;24(1):706. doi: 10.1186/s12885-024-12388-2. PMID: 38851712Free PMC Article
The Molecular Mechanisms of Actions, Effects, and Clinical Implications of PARP Inhibitors in Epithelial Ovarian Cancers: A Systematic Review.
Lau CH, Seow KM, Chen KH
Int J Mol Sci 2022 Jul 23;23(15) doi: 10.3390/ijms23158125. PMID: 35897700Free PMC Article
Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update.
Henry NL, Somerfield MR, Dayao Z, Elias A, Kalinsky K, McShane LM, Moy B, Park BH, Shanahan KM, Sharma P, Shatsky R, Stringer-Reasor E, Telli M, Turner NC, DeMichele A
J Clin Oncol 2022 Sep 20;40(27):3205-3221. Epub 2022 Jun 27 doi: 10.1200/JCO.22.01063. PMID: 35759724
ESMO recommendations on predictive biomarker testing for homologous recombination deficiency and PARP inhibitor benefit in ovarian cancer.
Miller RE, Leary A, Scott CL, Serra V, Lord CJ, Bowtell D, Chang DK, Garsed DW, Jonkers J, Ledermann JA, Nik-Zainal S, Ray-Coquard I, Shah SP, Matias-Guiu X, Swisher EM, Yates LR
Ann Oncol 2020 Dec;31(12):1606-1622. Epub 2020 Sep 28 doi: 10.1016/j.annonc.2020.08.2102. PMID: 33004253
BRCA Mutations, DNA Repair Deficiency, and Ovarian Aging.
Oktay K, Turan V, Titus S, Stobezki R, Liu L
Biol Reprod 2015 Sep;93(3):67. Epub 2015 Jul 29 doi: 10.1095/biolreprod.115.132290. PMID: 26224004Free PMC Article

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