Error-Prone DNA Repair Implicated in Analysis of Cancer Mutation Signature Clusters

NEW YORK (GenomeWeb) – A research duo has looked at tumor mutation clusters for clues to the mutagenic processes contributing to various cancer types.

“Clustered mutations are likely to be generated at the same moment in time, so by looking at several neighboring mutations at once, we can have a better understanding of what has damaged the DNA,” first author Fran Supek, a group leader at Barcelona Institute of Science and Technology’s Centre for Genomic Regulation (CRG), said in a statement. “[W]e show that focusing on patterns of clustered mutations and using a large number of cancer genomes, we can identify the culprits that cause mutations in tumors.”

Supek and senior author Ben Lehner, a researcher affiliated with the CRG and Pompeu Fabra University, analyzed genome sequences for more than 1,000 tumors sequenced for the Cancer Genome Atlas and other efforts, searching for clustered mutations and mutation signatures that might point to mechanisms driving these genetic alterations. Their analysis led to nine clustered mutation signatures.

Along with mutation signatures associated with tobacco exposure or exposure to other known carcinogens, the team saw a signature that seemed to mark a switch from error-free mismatch DNA repair to an error-prone version of

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