Preprint: copy-number mutational signatures can be extracted from targeted gene panels and retain prognostic relevance

Copy-number (CN) mutational signatures — recurring patterns of genomic gain and loss thought to reflect underlying mutational processes — have typically been characterised using whole-genome or whole-exome sequencing. Targeted gene panels (TGPs), which sequence a defined subset of cancer-relevant genes, dominate routine clinical sequencing, but whether CN signatures can be reliably extracted from TGP data has remained unclear.

A bioRxiv preprint addresses this question using two real-world TGP cohorts comprising 1,726 patients across 62 tumour types, of which 825 had associated clinical outcome data. The authors report that TGP-derived CN signatures recapitulated established biological associations seen in genome-wide studies, including links to homologous recombination deficiency and TP53 alterations. Critically, the signatures also associated with patient outcomes in the clinically annotated subset, suggesting that prognostically relevant information is not entirely lost when using TGPs rather than broader assays.

The authors have made the underlying data publicly available, which will facilitate independent validation. The study has not yet been peer reviewed.

This is of interest to researchers in cancer genomics and computational oncology, and to oncologists who use or evaluate TGP-based sequencing platforms. It also has methodological relevance to those designing or interpreting biomarker studies in routine clinical sequencing settings.