# Enabling characteristic: genome instability and mutation

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

## TL;DR

Cancers mutate faster than normal cells because their DNA repair and chromosome segregation are broken. This fuels every other hallmark.

## Summary

Genome instability and mutation is the enabling characteristic that lets cancers mutate faster than normal cells because DNA repair and chromosome segregation are broken, fuelling every other hallmark. Its forms are defective mismatch repair (MSI), homologous recombination deficiency (BRCA and HRD), replication stress and chromosomal instability, covered in the DNA damage response, DNA replication stress and Chromosomal instability & aneuploidy pathways and the Whole-genome doubling (WGD) entry. It is exploited by PARP inhibitors guided by HRD & BRCA testing, by platinum, by immunotherapy for MSI-H and TMB-high tumours and by emerging CIN-directed drugs, with BRCA1 / BRCA2, PARP, ATR and TP53 as targets. Readers reach it from the Hallmarks of Cancer overview and the mutagenesis pathway.

## Fields

- Kind: Term
- Last checked: 2026-09-08
- Tags: hallmark

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer
- Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022): https://doi.org/10.1158/2159-8290.CD-21-1059

## Connected records

- technologies: [HRD & BRCA testing](https://onco.cc/technologies/hrd-testing/), [PARP inhibitors](https://onco.cc/technologies/parp-inhibitor/)
- targets: [ATR](https://onco.cc/targets/atr/), [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/), [PARP](https://onco.cc/targets/parp/), [TP53](https://onco.cc/targets/tp53/)
- pathways: [Chromosomal instability & aneuploidy](https://onco.cc/pathways/chromosomal-instability/), [DNA damage response & homologous recombination](https://onco.cc/pathways/ddr/), [DNA replication stress](https://onco.cc/pathways/replication-stress/), [Mutagenesis & mutational signatures](https://onco.cc/pathways/mutagenesis-signatures/)
- terms: [Aneuploidy and chromosomal instability as the cause of cancer](https://onco.cc/terms/aneuploidy-theory-of-cancer/), [Hallmarks of Cancer](https://onco.cc/terms/hallmarks-of-cancer/), [Hallmarks of cancer as a synthesis of the theories](https://onco.cc/terms/hallmarks-synthesis/), [Homologous recombination deficiency (HRD)](https://onco.cc/terms/hrd/), [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/), [Mutational signature](https://onco.cc/terms/mutational-signature/), [Tumour mutational burden (TMB)](https://onco.cc/terms/tmb/), [Whole-genome doubling (WGD)](https://onco.cc/terms/whole-genome-doubling/)
- key papers: [The Hallmarks of Cancer: six capabilities every tumour must acquire](https://onco.cc/key-papers/paper-hallmarks-of-cancer-cell-2000/)

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