Science: Large-scale cancer WGS data reveal dozens of new mutational signatures

In what is said to be the largest study of its kind, a team of researchers led by Cambridge University Hospitals (CUH) and the University of Cambridge has uncovered a "treasure" about the causes of cancer

The findings, published in the journal Science ("Alternative mutational signatures in cancer with whole-genome sequence sequences in the UK population"), revealed dozens of previously unreported mutational signatures, including tumor-specific rare ones

Lead author Dr Andrea Degasperi, Associate Research Fellow at the University of Cambridge, said: "Whole genome sequencing has given us an overall picture of all the mutations that cause cancer in every individual

Globally, cancer is the No.

"With the exception of a few disease-causing driver mutations, WGS allows exploration of the complete picture of passenger mutations that describe processes that arise during tumorigenesis, resulting in patterns known as mutational signatures," the authors comment

Degasperi and colleagues performed mutational signature analysis on 12,222 WGS cancer patients from the NHS Centre for Genomic Medicine in the UK as part of the UK Genomics 100,000 Genomes Project

The results suggest that for each tumor type, cancers may have a limited number of common mutational signatures and some rare ones that occur less frequently in the population

They also identified 58 new mutational signatures, including 40 single-base substitution (SBS) and 18 double-base substitution (DBS) mutational signatures, suggesting that there are other carcinogenic causes that we don't fully understand

The team also developed a computer algorithm that can look for mutational signatures in new samples

Nick Zainer, Professor of Genomic Medicine and Bioinformatics at the University of Cambridge and Honorary Consultant in Clinical Genetics at CUH, said: "Identifying mutational signatures is important because they are like crime scene fingerprints - they help identify the culprit of cancer.

"Thanks to samples from patients and clinicians across the UK, we were able to carry out forensic analysis of over 12,000 NHS cancer genomes

Notably, the authors concluded: "The current analysis introduces the concept of common versus rare features in each tumor type

"This study shows how powerful the WGS test is at providing clues as to how cancer may develop, how it behaves and which treatment options are most effective

Matt Brown, CSO of Genomics England, added: "Mutational signatures are an example of how the full potential of WGS