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New oncogene gives valuable insight into hepatocellular tumors in humans
Date:4/23/2009

rch for mutations, GP130 exons were screened in all samples and the function of 7 different mutants was analysed in HEP3B.

A somatic mutation was identified in 65% of the IHCA including 24 different small in-frame deletions or duplications. A spectrum of mutations shows that mutations clearly target the IL-6 binding site in GP130. Also demonstrated was the fact that the expression of the most frequent GP130 mutants in HEP3B cells activates STAT3 in absence of IL-6. The researchers searched for possible interaction and cooperation of GP130 activation with other pathways altered in hepatocellular adenoma. HNF1α inactivation and gp130 activation were mutually exclusive in HCA (P< 10-4). By contrast, in half of the -catenin activating HCA, a GP130-activating mutation was identified. For two IHCA associated with a malignant transformation, both an activating gp130 and -catenin mutations were found. Further, analysis of 220 hepatocellular carcinomas revealed rare GP130 alterations in all cases accompanied by -catenin-activating mutations, suggesting a cooperative effect of these signalling pathways in the malignant transformation of hepatocytes.


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Contact: Camilla Dormer
easlpressoffice@cohnwolfe.com
44-787-619-0439
European Association for the Study of the Liver
Source:Eurekalert

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