# BRCA reversion mutations

Source: https://onco.cc/terms/brca-reversion-mutations/  
OnCo record `brca-reversion-mutations` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A cancer with a broken BRCA gene can repair the break itself under the pressure of PARP inhibitors or platinum: a second mutation restores the reading frame, the DNA-repair machinery switches back on, and both drugs stop working. Reversion mutations show up in blood ctDNA in a fifth to a third of resistant cases and mean it is time for a different class of treatment.

## Summary

What is measured: a second mutation in BRCA1, BRCA2 (or PALB2, RAD51C, RAD51D) that restores a functional protein in a tumour that had lost it. How: sequencing of a progression biopsy or, more often, plasma cell-free DNA with a panel covering the whole gene; the reversion appears as a deletion or insertion that puts the reading frame back, or a change that undoes the original variant, and it is frequently polyclonal. It is found in 20 to 40 percent of ovarian cancers and metastatic prostate cancers that have become resistant to PARP inhibitors or platinum, and less often in breast cancer; other resistance routes (loss of 53BP1 or the Shieldin complex, drug efflux, PARP1 mutations) are invisible to this test. Germline carriers keep their germline mutation in normal cells; the reversion is somatic. What a result changes: it predicts non-response to further PARP inhibition and to platinum, so treatment moves to taxanes, antibody-drug conjugates (mirvetuximab for folate receptor alpha-high ovarian cancer) or trials of ATR and POLQ inhibitors; its appearance in blood precedes radiographic progression; its absence supports PARP inhibitor rechallenge (OReO). Where it matters: platinum-sensitive and platinum-resistant ovarian cancer, high-grade serous ovarian cancer and metastatic castration-resistant prostate cancer.

## Fields

- Kind: Term
- Last checked: 2026-09-17
- Also known as: reversion mutation; reversion mutations; BRCA reversion; BRCA1 reversion; BRCA2 reversion; secondary BRCA mutation; restored homologous recombination; homologous recombination restoration; PARP inhibitor resistance mutation; acquired PARP inhibitor resistance; reversion to platinum resistance

## Connected records

- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/), [Germline BRCA mutation (gBRCA)](https://onco.cc/terms/gbrca-mutation/), [Homologous recombination deficiency (HRD)](https://onco.cc/terms/hrd/), [Platinum-sensitive / platinum-resistant](https://onco.cc/terms/platinum-sensitivity/)
- targets: [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/), [PARP](https://onco.cc/targets/parp/)
- drugs: [Niraparib](https://onco.cc/drugs/niraparib/), [Olaparib](https://onco.cc/drugs/olaparib/), [Rucaparib](https://onco.cc/drugs/rucaparib/)
- cancers: [High-grade serous ovarian cancer](https://onco.cc/cancers/high-grade-serous-ovarian-cancer/), [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Platinum-resistant ovarian cancer](https://onco.cc/cancers/platinum-resistant-ovarian-cancer/), [Platinum-sensitive ovarian cancer](https://onco.cc/cancers/platinum-sensitive-ovarian-cancer/)

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