Loading
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.
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.
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.
Shares Intraductal carcinoma of the prostate (IDC-P), Germline BRCA mutation (gBRCA), Double-strand break repair: HR versus end joining, Homologous recombination deficiency (HRD).
Shares Germline BRCA mutation (gBRCA), Double-strand break repair: HR versus end joining, Homologous recombination deficiency (HRD), Germline vs somatic mutations.
Shares Germline BRCA mutation (gBRCA), Double-strand break repair: HR versus end joining, Homologous recombination deficiency (HRD), Germline vs somatic mutations.
Shares Germline BRCA mutation (gBRCA), Double-strand break repair: HR versus end joining, Homologous recombination deficiency (HRD), Germline vs somatic mutations.
Shares Double-strand break repair: HR versus end joining, Homologous recombination deficiency (HRD), Germline vs somatic mutations, Whole-exome & whole-genome sequencing.
Shares Germline BRCA mutation (gBRCA), Double-strand break repair: HR versus end joining, Homologous recombination deficiency (HRD), Germline vs somatic mutations.
Shares Germline BRCA mutation (gBRCA), Double-strand break repair: HR versus end joining, Germline vs somatic mutations, BRCA1 / BRCA2 (HRD).
Shares Chromosomal instability & aneuploidy, Germline BRCA mutation (gBRCA), Double-strand break repair: HR versus end joining, Homologous recombination deficiency (HRD).