PMID- 17150109 OWN - NLM STAT- MEDLINE DCOM- 20070108 LR - 20181113 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 6 DP - 2006 Dec 6 TI - A novel mutation in the tyrosine kinase domain of ERBB2 in hepatocellular carcinoma. PG - 278 AB - 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. FAU - Bekaii-Saab, Tanios AU - Bekaii-Saab T AD - Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA. Tanios.Bekaii-Saab@osumc.edu FAU - Williams, Nita AU - Williams N FAU - Plass, Christoph AU - Plass C FAU - Calero, Miguel Villalona AU - Calero MV FAU - Eng, Charis AU - Eng C LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061206 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Carcinoma, Hepatocellular/*enzymology/*genetics MH - Genes, erbB-2/genetics MH - Humans MH - Liver Neoplasms/*enzymology/*genetics MH - Mutation, Missense/*genetics MH - Protein-Tyrosine Kinases/*genetics MH - Receptor, ErbB-2/*genetics/metabolism PMC - PMC1712353 EDAT- 2006/12/08 09:00 MHDA- 2007/01/09 09:00 PMCR- 2006/12/06 CRDT- 2006/12/08 09:00 PHST- 2006/08/24 00:00 [received] PHST- 2006/12/06 00:00 [accepted] PHST- 2006/12/08 09:00 [pubmed] PHST- 2007/01/09 09:00 [medline] PHST- 2006/12/08 09:00 [entrez] PHST- 2006/12/06 00:00 [pmc-release] AID - 1471-2407-6-278 [pii] AID - 10.1186/1471-2407-6-278 [doi] PST - epublish SO - BMC Cancer. 2006 Dec 6;6:278. doi: 10.1186/1471-2407-6-278.