# Homologous recombination repair gene mutation in prostate cancer

Source: https://onco.cc/biomarkers/hrr-gene-mutation/  
OnCo record `hrr-gene-mutation` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A fault in one of the genes a cell uses to mend broken DNA. It decides whether a PARP inhibitor can be prescribed, but the list of genes that counts is different for each of the four approved routes, and the evidence behind them is mostly evidence about BRCA2.

## Summary

Between a fifth and a quarter of metastatic prostate cancers carry an alteration in this gene set: BRCA2, BRCA1 and ATM aberrations alone were 19.3% of 150 castration-resistant tumours (Robinson 2015). About half of that is inherited: germline mutations in 20 DNA repair genes were present in 82 of 692 men with metastatic disease, 11.8%, led by BRCA2 at 5.3%, ATM at 1.6%, CHEK2 at 1.9% and BRCA1 at 0.9%, with no difference by family history or age at diagnosis (Pritchard 2016). The four approved routes ask for four different gene lists. Olaparib alone names 14 genes; olaparib with abiraterone names BRCA1 and BRCA2 only; rucaparib names BRCA1 and BRCA2 only; niraparib with abiraterone names BRCA2 alone in castration-sensitive disease and BRCA1 or BRCA2 in castration-resistant disease; talazoparib with enzalutamide names 12 genes, six of which are not on olaparib's list, including MLH1, a mismatch repair gene, and the label states that no FDA-approved test for detecting them with talazoparib is currently available. The response data do not spread evenly across those lists: in PROfound, confirmed objective response among men with a single-gene alteration and measurable disease was 24 of 43 with BRCA2 (56%), 3 of 30 with ATM (10%) and 2 of 34 with CDK12 (6%).

## Fields

- Kind: Biomarker
- Last checked: 2026-09-25
- Also known as: HRR gene mutation; HRRm; HRR-mutated; homologous recombination repair mutation; DNA repair gene mutation; BRCA2 prostate; ATM prostate; CDK12 prostate
- Tags: biomarker; prostate

## Sources

- LYNPARZA prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=741ff3e3-dc1a-45a6-84e5-2481b27131aa
- TALZENNA prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c6fd147f-a77e-4a0b-9280-e82ecc41b4be
- AKEEGA prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8245a990-3268-4613-b5c5-9537858a1eb9
- RUBRACA prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0295d202-1cfe-7659-e063-6294a90a476e
- Pritchard et al., N Engl J Med 2016: inherited DNA-repair gene mutations in 692 men with metastatic prostate cancer unselected for family history: https://doi.org/10.1056/NEJMoa1603144

## Connected records

- biomarkers: [Circulating tumour DNA fraction (and what a negative plasma result means)](https://onco.cc/biomarkers/ctdna-tumour-fraction/), [Germline BRCA1/2 pathogenic variant (gBRCAm)](https://onco.cc/biomarkers/brca-germline/), [HRD-positive (genomic instability score)](https://onco.cc/biomarkers/hrd-positive/), [Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations](https://onco.cc/biomarkers/brca-somatic/)
- cancers: [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Metastatic hormone-sensitive prostate cancer](https://onco.cc/cancers/prostate-mhspc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [PARP inhibitors](https://onco.cc/technologies/parp-inhibitor/)
- targets: [ATM](https://onco.cc/targets/atm/), [BARD1](https://onco.cc/targets/bard1/), [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/), [BRIP1](https://onco.cc/targets/brip1/), [CDK12](https://onco.cc/targets/cdk12/), [CHEK2](https://onco.cc/targets/chek2/), [PALB2](https://onco.cc/targets/palb2/), [PARP](https://onco.cc/targets/parp/), [RAD51C](https://onco.cc/targets/rad51c/), [RAD51D](https://onco.cc/targets/rad51d/)
- drugs: [Niraparib](https://onco.cc/drugs/niraparib/), [Olaparib](https://onco.cc/drugs/olaparib/), [Rucaparib](https://onco.cc/drugs/rucaparib/), [Talazoparib](https://onco.cc/drugs/talazoparib/)
- pathways: [Base excision repair, PARP & alkylation damage](https://onco.cc/pathways/base-excision-repair-parp/), [DNA damage response & homologous recombination](https://onco.cc/pathways/ddr/), [Double-strand break repair: HR versus end joining](https://onco.cc/pathways/homologous-recombination-repair/), [Synthetic lethality: paired dependencies](https://onco.cc/pathways/synthetic-lethality-map/)
- terms: [BRCA reversion mutations](https://onco.cc/terms/brca-reversion-mutations/), [Castration-resistant prostate cancer (CRPC)](https://onco.cc/terms/castration-resistance/), [Germline BRCA mutation (gBRCA)](https://onco.cc/terms/gbrca-mutation/), [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/), [Homologous recombination deficiency (HRD)](https://onco.cc/terms/hrd/), [Synthetic lethality](https://onco.cc/terms/synthetic-lethality/), [Variant of uncertain significance (VUS)](https://onco.cc/terms/vus/)
- key papers: [Analysis of circulating cell-free DNA identifies multiclonal heterogeneity of BRCA2 reversion mutations associated with resistance to PARP inhibitors](https://onco.cc/key-papers/paper-quigley-brca2-reversion-cfdna-parp-resistance-cancer-discov-2017/), [Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference](https://onco.cc/key-papers/paper-jensen-clonal-haematopoiesis-cfdna-interference-prostate-jama-oncol-2021/), [Inherited DNA-repair gene mutations in men with metastatic prostate cancer](https://onco.cc/key-papers/paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016/), [SU2C-PCF: integrative clinical genomics of advanced prostate cancer](https://onco.cc/key-papers/paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015/), [TRITON2: rucaparib in men with metastatic castration-resistant prostate cancer harbouring a BRCA1 or BRCA2 alteration](https://onco.cc/key-papers/paper-abida-triton2-rucaparib-brca-jco-2020/)

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