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Comparative Study
. 2006 Dec 6:6:278.
doi: 10.1186/1471-2407-6-278.

A novel mutation in the tyrosine kinase domain of ERBB2 in hepatocellular carcinoma

Tanios Bekaii-Saab  1 , Nita Williams, Christoph Plass, Miguel Villalona Calero, Charis Eng
Affiliations
Comparative Study

A novel mutation in the tyrosine kinase domain of ERBB2 in hepatocellular carcinoma

Tanios Bekaii-Saab et al. BMC Cancer. .

Abstract

Background: Several studies showed that gain-of-function somatic mutations affecting the catalytic domain of EGFR in non-small cell lung carcinomas were associated with response to gefitinib and erlotinib, both EGFR-tyrosine kinase inhibitors. In addition, 4% of non-small cell lung carcinomas were shown to have ERBB2 mutations in the kinase domain. In our study, we sought to determine if similar respective gain-of-function EGFR and ERBB2 mutations were present in hepatoma and/or biliary cancers.

Methods: We extracted genomic DNA from 40 hepatoma (18) and biliary cancers (22) samples, and 44 adenocarcinomas of the lung, this latter as a positive control for mutation detection. We subjected those samples to PCR-based semi-automated double stranded nucleotide sequencing targeting exons 18-21 of EGFR and ERBB2. All samples were tested against matched normal DNA.

Results: We found 11% of hepatoma, but no biliary cancers, harbored a novel ERBB2 H878Y mutation in the activating domain.

Conclusion: These newly described mutations may play a role in predicting response to EGFR-targeted therapy in hepatoma and their role should be explored in prospective studies.

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Figures

Figure 1
Figure 1
Somatic missense mutation, H878Y, found in genomic DNA from hepatoma (top chromatogram) but not in corresponding normal tissue (bottom panel).
See this image and copyright information in PMC

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