Evolutionary Analysis Reveals Number, Nature of Mutations Under Positive Selection in Cancer

NEW YORK (GenomeWeb) – By analyzing genomic data for thousands of tumors, a team from the UK and Belgium has concluded that as few as one mutation and as many as 10 can spur cancer development, depending on the cancer type and genes affected.

Researchers from the Wellcome Trust Sanger Institute, the University of Cambridge, and elsewhere took a molecular evolution-informed approach to examine positive and negative selection patterns — along with the alterations driving cancer formation — in more than 7,600 tumors. Their findings, published online today in Cell, indicate that many mutations are tolerated and not subjected to negative selection, while positive selection plays a prominent role in cancer formation.

When the team focused on cancer driver mutations falling in protein-coding sequences in the tumor collection, it found that four substitution mutations are typically subjected to positive selection in cancer, on average. Still, the number of driver mutations under positive selection varied dramatically between the 29 cancer types considered, ranging from one or fewer coding mutations per thyroid or testicular tumor to almost 10 tumor drivers in cancer types such as colorectal cancer or endometrial cancer.

The research shows that “across cancer types a relatively consistent small number

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