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Sequencing 104 triple-negative breast cancers at diagnosis showed they range from tumours with a handful of mutations to tumours with hundreds, that only about a third of mutations are even expressed, and that TP53, PIK3CA and PTEN are the changes present in most of the tumour's cells.
104 primary TNBCs were profiled by exome and RNA sequencing with deep re-sequencing of 2,414 somatic mutations to measure clonal frequency. The cancers showed a wide, continuous spectrum of genomic evolution; about 36% of mutations were expressed. Basal TNBC showed more variation in clonal frequencies than non-basal TNBC. TP53, PIK3CA and PTEN mutations were clonally dominant compared with other genes, though in some tumours their frequencies were incompatible with founder status; mutations in cytoskeletal, cell-shape and motility genes occurred at lower clonal frequency, suggesting later acquisition.
The cohort is deposited as brca_bccrc (British Columbia, Nature 2012) on cBioPortal.
The first TNBC-specific genome paper established that the disease has no shared driver beyond TP53 and that each tumour is a clonal mixture, the reason single-target drugs have struggled and ctDNA tracking needs patient-specific variants.
Shares PTEN, Nature, PIK3CA / PI3K-alpha, TP53.
Shares PIK3CA / PI3K-alpha, TP53, Triple-negative breast cancer (TNBC).
Shares Clonal evolution & minimal residual disease, Nature, TP53, Triple-negative breast cancer (TNBC).
Shares Next-generation sequencing (NGS), TP53.
Shares PTEN, PIK3CA / PI3K-alpha, Triple-negative breast cancer (TNBC).
Shares PTEN, PIK3CA / PI3K-alpha, Triple-negative breast cancer (TNBC).
Shares PTEN, PIK3CA / PI3K-alpha, Triple-negative breast cancer (TNBC).
Shares PTEN, PIK3CA / PI3K-alpha, TP53, Triple-negative breast cancer (TNBC).