What 2,023 whole genomes reveal about bowel cancer — and why it changes the map

The study

Using the UK 100,000 Genomes Project, researchers performed whole-genome sequencing (WGS) on 2,023 colorectal cancers — the most detailed genomic picture of this common cancer to date. WGS reads the entire genome, not just a shortlist of known cancer genes, so it can surface drivers and patterns that targeted panels miss.

What they found

• 250+ putative driver genes, many never previously linked to colorectal cancer — including recurrent changes outside the protein-coding genome, a region standard testing ignores.
• Four new common subgroups of microsatellite-stable cancer, defined by genomic features such as whole-genome doubling and chromosomal instability — each carrying independent prognostic information.
• Rare but clinically relevant subgroups, including tumours showing both microsatellite and chromosomal instability.
• Clues to cause: a mutational signature linking E. coli colibactin to rectal cancers, and the SBS93 signature pointing to diet or smoking as a risk factor.
• Near-universal immune escape in heavily mutated tumours, and in about half of microsatellite-stable cancers — often via HLA copy-number changes, which bears on immunotherapy response.
• Many drivers are actionable (for example BRCA1, IDH1) — an existing or trial drug may target them.

Why it matters

This is the clearest evidence yet that whole-genome sequencing adds clinical value over targeted panels in a common cancer: new prognostic subgroups, actionable rare variants, and aetiological signals — diet, smoking, a bacterial toxin — all emerged from reading the whole genome. It is also a proof point for the NHS's national sequencing infrastructure.