{"entity":{"id":"paper-taylor-germline-brca2-evolutionary-trajectories-nat-commun-2017","kind":"paper","name":"Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories","aka":[],"tldr":"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.","asOf":"2026-09-25","links":[{"label":"Taylor et al., Nat Commun 2017: genomes and methylomes of localised prostate cancer from 14 germline BRCA2 carriers, with microdissection of intraductal carcinoma","url":"https://doi.org/10.1038/ncomms13671"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28067867/"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":["wes-wgs"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair","chromosomal-instability","clonal-evolution"],"terms":["germline-vs-somatic","gbrca-mutation","hrd","intraductal-carcinoma-prostate"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2017,"doi":"10.1038/ncomms13671","pmid":"28067867","authors":"Taylor RA, Fraser M, Livingstone J, et al.","paperType":"basic","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."],"whatItMeans":"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."],"changedPractice":false,"participants":14},"route":"/key-papers/paper-taylor-germline-brca2-evolutionary-trajectories-nat-commun-2017/","neighbours":{"cancer":[{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"target":[{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"}],"pathway":[{"id":"chromosomal-instability","kind":"pathway","name":"Chromosomal instability & aneuploidy","route":"/pathways/chromosomal-instability/"},{"id":"clonal-evolution","kind":"pathway","name":"Clonal evolution & minimal residual disease","route":"/pathways/clonal-evolution/"},{"id":"homologous-recombination-repair","kind":"pathway","name":"Double-strand break repair: HR versus end joining","route":"/pathways/homologous-recombination-repair/"}],"term":[{"id":"gbrca-mutation","kind":"term","name":"Germline BRCA mutation (gBRCA)","route":"/terms/gbrca-mutation/"},{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"hrd","kind":"term","name":"Homologous recombination deficiency (HRD)","route":"/terms/hrd/"},{"id":"intraductal-carcinoma-prostate","kind":"term","name":"Intraductal carcinoma of the prostate (IDC-P)","route":"/terms/intraductal-carcinoma-prostate/"}],"journal":[{"id":"nature-communications","kind":"journal","name":"Nature Communications","route":"/journals/nature-communications/"}]}}