A novel mutation in the tyrosine kinase domain of ERBB2 in hepatocellular carcinoma
1 Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
2 Department of Pharmacology, The Ohio State University, Columbus, Ohio, USA
3 Division of Human Genetics, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
4 Department of Molecular Virology, Immunology and Medical Genetics; Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
5 Genomic Medicine Institute and Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio, USA
BMC Cancer 2006, 6:278 doi:10.1186/1471-2407-6-278Published: 6 December 2006
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.
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.
We found 11% of hepatoma, but no biliary cancers, harbored a novel ERBB2 H878Y mutation in the activating domain.
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.