Loading
Sequencing 617 metastatic breast cancers showed they carry more mutations and more clonal diversity than early tumours, and that metastatic triple-negative cancers have somatic loss of both copies of a homologous recombination gene in 7% against 2% of early ones.
The landscape of somatic alterations was investigated in 617 metastatic breast cancers. Nine driver genes (TP53, ESR1, GATA3, KMT2C, NCOR1, AKT1, NF1, RIC8A, RB1) were more frequently mutated in hormone receptor-positive, HER2-negative metastatic cancers (381) than in early cancers from TCGA, with 18 enriched amplicons and increased mutational signatures S2, S3, S10, S13 and S17; TP53, RB1 and NF1 mutations and S10, S13 and S17 marked poor outcome. Metastatic TNBCs showed an increased frequency of somatic biallelic loss-of-function mutations in homologous recombination DNA repair genes compared with early TNBC (7% versus 2%). Metastatic cancers showed increased mutational burden and clonal diversity.
Re-biopsy and re-sequencing at relapse can find repair defects and a higher mutation burden that the primary did not show, which matters for PARP inhibitor and immunotherapy eligibility in metastatic TNBC.
Shares Clonal evolution & minimal residual disease, Nature, TP53, Triple-negative breast cancer (TNBC).
Shares BRCA1 / BRCA2 (HRD), TP53, Triple-negative breast cancer (TNBC), HR-positive / HER2-negative breast cancer.
Shares RB1, Nature, TP53, Triple-negative breast cancer (TNBC).
Shares BRCA1 / BRCA2 (HRD), Metastatic triple-negative breast cancer, Triple-negative breast cancer (TNBC), HR-positive / HER2-negative breast cancer.
Shares NF1 (neurofibromin), RB1, TP53, Triple-negative breast cancer (TNBC).
Shares Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations, Double-strand break repair: HR versus end joining, BRCA1 / BRCA2 (HRD), Triple-negative breast cancer (TNBC).
Shares Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations, BRCA1 / BRCA2 (HRD), Triple-negative breast cancer (TNBC).
Shares BRCA1 / BRCA2 (HRD), TP53, Triple-negative breast cancer (TNBC).