The mutREAD method detects mutational signatures from low quantities of cancer DNA.

Mutational processes acting on cancer genomes can be traced by investigating mutational signatures. Because high sequencing costs limit current studies to small numbers of good-quality samples, we propose a robust, cost- and time-effective method, called mutREAD, to detect mutational signatures from small quantities of DNA, including degraded samples. We show that mutREAD recapitulates mutational signatures identified by whole genome sequencing, and will ultimately allow the study of mutational signatures in larger cohorts and, by compatibility with formalin-fixed paraffin-embedded samples, in clinical settings. Sequencing tumour genomes can reveal information about the processes that drive the formation of cancer. Here, the authors describe a method that can detect these mutational signatures from small amounts of DNA and degraded samples.