# Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories

Source: https://onco.cc/key-papers/paper-taylor-germline-brca2-evolutionary-trajectories-nat-commun-2017/  
OnCo record `paper-taylor-germline-brca2-evolutionary-trajectories-nat-commun-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Reading the whole genomes of localised prostate cancers from 14 men who had inherited a BRCA2 fault found tumours that already looked like advanced disease while still confined to the prostate.

## Summary

The genomes and methylomes of localised prostate cancer from 14 carriers of deleterious germline BRCA2 mutations were profiled. BRCA2-mutant prostate cancers showed increased genomic instability and a mutational profile that more closely resembled metastatic than localised disease. They showed genomic and epigenomic dysregulation of the MED12L and MED12 axis, which is frequently dysregulated in metastatic castration-resistant prostate cancer, and this dysregulation was enriched in BRCA2-mutant tumours containing intraductal carcinoma. Microdissection and sequencing of intraductal carcinoma and the juxtaposed adjacent non-intraductal invasive carcinoma in 10 patients demonstrated a common ancestor to both histopathologies.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Nature Communications
- Year: 2017
- DOI: 10.1038/ncomms13671
- Authors: Taylor RA, Fraser M, Livingstone J, et al.
- Findings: Localised BRCA2-mutant prostate cancers showed greater genomic instability and a metastatic-like mutational profile.; Dysregulation of the MED12L and MED12 axis, enriched in tumours containing intraductal carcinoma.; Intraductal carcinoma and the adjacent invasive carcinoma share a common ancestor on microdissection of 10 cases.
- What it means: It supplies the biological reason for treating a BRCA2 carrier's localised disease aggressively rather than watching it, and it settles a long-standing pathology question by showing that intraductal carcinoma and the adjacent invasive tumour are the same clone rather than two separate processes.
- Caveats: Fourteen genomes, so gene-level claims rest on very small numbers.; Localised disease from carriers identified through genetics services.; MED12L has no therapeutic consequence.

## Sources

- Taylor et al., Nat Commun 2017: genomes and methylomes of localised prostate cancer from 14 germline BRCA2 carriers, with microdissection of intraductal carcinoma: https://doi.org/10.1038/ncomms13671
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28067867/

## Connected records

- cancers: [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Whole-exome & whole-genome sequencing](https://onco.cc/technologies/wes-wgs/)
- targets: [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/)
- pathways: [Chromosomal instability & aneuploidy](https://onco.cc/pathways/chromosomal-instability/), [Clonal evolution & minimal residual disease](https://onco.cc/pathways/clonal-evolution/), [Double-strand break repair: HR versus end joining](https://onco.cc/pathways/homologous-recombination-repair/)
- terms: [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/), [Intraductal carcinoma of the prostate (IDC-P)](https://onco.cc/terms/intraductal-carcinoma-prostate/)
- journals: [Nature Communications](https://onco.cc/journals/nature-communications/)

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