Mutational signature
A characteristic pattern of mutations that reveals what caused them: tobacco, UV, a broken repair gene.
COSMIC signatures (SBS1 ageing, SBS3 HRD, SBS4 tobacco, SBS7 UV, SBS2/13 APOBEC, SBS6/15 MMR). Signature 3 identifies HRD beyond BRCA; APOBEC signatures predict certain resistance mutations. Requires WGS or WES.
Cancers are defined as much by the tissue they come from as by the mutations they carry, which is why the same drug can work in one organ and fail in another with the same mutation. TCGA is the shared public dataset behind most modern biomarkers and target discovery.
Carrying a cancer mutation is normal; most mutant clones never become cancer. This means blood or tissue tests that look for driver mutations alone will produce false positives, and that the question of what tips a mutant clone into cancer (tissue environment, further hits, immune surveillance) is as important as the mutation itself.
There are not thousands of cancer genes, and any one patient's tumour is driven by only a few of them. That makes targeted sequencing panels sensible, but because most drivers are lost tumour suppressors, drugs exist for only a minority, which is why the same group turned to early detection.