UK researchers have mapped the full range of mutations across 16 cancer types in a study published in Nature Genetics. Part of Genomics England’s 100,000 Genomes Project, the research analyzed the whole genomes of nearly 11,000 NHS patients, identifying 134 mutational signatures—genetic “fingerprints” left by DNA damage, including 26 previously unknown.
Beyond single-letter DNA changes, the study examined complex mutations to reconstruct a tumor’s genetic history. It revealed that 16% of breast cancers and 14% of ovarian cancers show homologous recombination deficiency (HRD), suggesting thousands more patients could benefit from PARP inhibitors or platinum-based chemotherapy beyond those identified by standard BRCA testing.
The research also found a mutational signature in bowel cancer linked to E. coli toxins, more common in younger patients, shedding light on early-onset disease. Co-lead Professor David Wedge highlighted that decoding these genetic “scars” can guide more precise, individualized treatment, paving the way for improved outcomes in personalized oncology.