Liver Cancer Genomes Reveal Mutational Signatures Associated With Alcohol, Other Factors

NEW YORK (GenomeWeb) – A French research team has outlined mutational signatures associated with alcohol use and other environmental exposures in liver cancer using a large tumor genome collection.

The researchers tapped into more than 250 available liver cancer genome sequences — analyzed alongside dozens of new liver cancer genomes — for a study published online today in Nature Communications. From these data, they teased out 16 signatures with apparent ties to environmental exposures, including 10 mutational signatures and six signatures marked by specific structural rearrangements.

Along with signatures already described in other cancer types, the team noted that the so-called signature 16 profile appeared to be specific to liver cancer. That signature, which was characterized by enhanced mutation to the CTNNB1 gene and transcription-coupled damage, was particularly common in tumors from men with liver cancer and/or in individuals with a history of alcohol or tobacco use.

Senior author Jessica Zucman-Rossi, a researcher affiliated with INSERM, Paris Descartes University, and other centers, and her colleagues wrote that based on their results, “signature 16 is the real hallmark of liver cancers, operative in every tumor and accounting on average for 40 percent of all somatic mutations.” They further noted that they

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