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Frequent Genetic Mutations In Hepatocellular Carcinoma

The main risk factors for hepatocellular carcinoma (the most frequent liver cancer) are now relatively well known (infection by hepatitis B or C virus, alcoholic cirrhosis, etc.), but the underlying mechanisms are poorly understood. Research by Christine Perret and coworkers (INSERM 129, directed by Axel Kahn) shows that mutations in the gene encoding the protein beta-catenin are frequent in hepatocellular carcinoma. As these mutations have already been described in other cancers, this discovery points to their widespread involvement in carcinogenesis.

Recently, mutations in the gene coding for beta-catenin, a protein with a role in cell proliferation and adhesion, were identified in some patients with colorectal cancer and also in human melanoma cell lines. These mutations create a defective protein that can no longer be degraded and consequently accumulates inside cells. This build-up leads to uncontrolled cell proliferation, the characteristic process underlying cancer. INSERM research group 129 have now found that these mutations of the beta-catenin gene also occur in some cases of hepatocellular carcinoma in humans.

The team reached this conclusion after studying transgenic mice programmed to develop liver cancer: about 50% of the tumors that occurred in these mice contained the beta-catenin gene mutations. Turning to human liver cancer, the researchers then found that 8 (26%) out of 31 tumors contained malignant cells with the same mutations in the beta-catenin gene.

The discovery of frequent mutations in the beta-catenin gene in hepatocellular carcinoma raises the possibility of new therapeutic strategies targeting this protein.

This work by INSERM 129 was supported by the Ligue Nationale contre le Cancer, the Association pour la Recherche contre le Cancer (ARC) and the French Ministry of Research.

References:

"Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas" A. de La Coste1,
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Contact: Axel Kahn
perret@icgm.cochin.inserm.fr
33 1 44 41 24 12
French National Institute for Health and Medical Research (INSERM)
21-Jul-1998


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