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Somatic mutations are the DNA changes a tumour acquired during life; they are read from exome (protein-coding) or whole-genome sequencing of tumour and matched normal tissue.
Exome sequencing selects and sequences the protein-coding regions of all genes, about one to two percent of the genome (Wikipedia), and whole genome sequencing determines the entire DNA sequence at once. TCGA relied mainly on exomes, so its mutation data (distributed as MAF files) covers coding changes; whole genomes add non-coding and structural variants. Mutation data is sparse (most genes unmutated in most tumours), which is why it adds little to expression in many prediction tasks.
Showing the technology this term belongs to: Whole-exome & whole-genome sequencing.
It shows that the commonest driver event in advanced prostate cancer is invisible to the panels used to test for it, and that the shape of the structural damage in a genome tells you which repair pathway failed, which is information a mutation list does not carry.
It is the quantitative answer to why prostate cancer has so few targeted therapies. The common events are not druggable, the druggable ones are individually rare, and no trial can be powered on a driver present in 2% of men without an international basket.
It is the empirical basis for treating the two histologies as separate diseases for targeted therapy and as one disease for immunotherapy, which is exactly how they are treated.
With Moffitt's classical and basal-like split (the squamous and basal-like groups overlap) this fixed the molecular vocabulary of the disease and gave Precision-Panc and the UK's Glasgow group their trial framework.
Why small-cell lung cancer has no targeted therapy in the conventional sense: it is built from the loss of TP53 and RB1, and the drugs that transformed non-small-cell disease inhibit gains rather than restore losses. The NOTCH result pointed at DLL3 and, eventually, at tarlatamab.
The reference classification of prostate cancer as it presents, and the source of the two numbers that drive most molecular treatment decisions in the disease: a quarter with a PI3K or MAPK lesion, which is the rationale for capivasertib in PTEN-deficient disease, and a fifth with DNA repair inactivation, which is the rationale for PARP inhibitors.
It is the reference table the field still argues against, and it made two practical points that outlived it: a tumour with no driver on a standard panel usually has one that the panel did not look for, and pathway activity measured on protein does not follow from the mutation list.
It is the reference description of the disease and the source of the hypermutated split that decides who gets immunotherapy; it also put HER2 on the colorectal map as a drug target.
Shares Genomic hallmarks and structural variation in metastatic prostate cancer, Comprehensive genomic profiles of small cell lung cancer, Cancer AI vocabulary (CanSim terms map), Whole-exome & whole-genome sequencing and the tag cansim-terms.
Shares Targeted panel sequencing, Cancer AI vocabulary (CanSim terms map) and the tag cansim-terms.
Shares Variant calling, Cancer AI vocabulary (CanSim terms map) and the tag cansim-terms.
Shares Variant calling, Cancer AI vocabulary (CanSim terms map) and the tag cansim-terms.
Shares Cancer AI vocabulary (CanSim terms map), Pancreatic ductal adenocarcinoma, Colorectal cancer and the tag cansim-terms.
Shares Variant calling, Cancer AI vocabulary (CanSim terms map) and the tag cansim-terms.
Shares Variant calling, Cancer AI vocabulary (CanSim terms map) and the tag cansim-terms.
Shares Tumour mutational burden (TMB), Cancer AI vocabulary (CanSim terms map) and the tag cansim-terms.