A new study presented at The International Liver Congress™ 2015 in Vienna, Austria, showed that by using genomic analyses to understand how and when carcinogenic mutations occur in patients with hepatocellular carcinoma, it is possible to identify specific molecular profiles. It is hoped that these molecular profiles will help identify which patients would benefit from specific anticancer treatments.
Using exome sequencing, a technique for sequencing all the protein-coding genes in a genome, the study identified relationships between environmental exposures, such as tobacco smoke, alcohol use, and mutational patterns in hepatocellular carcinoma. It also determined the landscape of driver genes and pathways altered in different clinical stages and etiologic backgrounds. Out of eight mutational signatures identified in the study, two new mutational signatures for hepatocellular carcinoma were found.
Differentiating Mutational Processes
Jessica Zucman-Rossi, MD, PhD, Director of the INSERM/University Paris Descartes Functional Genomics of Solid Tumors Laboratory, explained, “Mutational signatures help with understanding the biological history of a cancer and can enable differentiation between ongoing mutational processes and historical ones. This helps identify potential new targets for anticancer therapies.”
In the study, most patients had at least one damaging alteration which could potentially be treated with either a U.S. Food and Drug Administration–approved drug (28% of patients) or an investigational drug (86% of patients) that has been studied in phase I to phase III clinical trials.
“Hepatocarcinogenesis is a multistep process in which precancerous lesions can ultimately transform into liver cancer. Genomic analyses, such as exome sequencing, allow us to better understand the mutational processes involved in the development of cancers. This detailed knowledge then helps us to unravel the mutagenic processes and to optimize personalized patient care,” said Markus Peck, MD, Secretary General, European Association for the Study of the Liver. ■