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

被引:43
作者
Bekaii-Saab, Tanios [1 ]
Williams, Nita
Plass, Christoph
Calero, Miguel Villalona
Eng, Charis
机构
[1] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Div Hematol & Oncol, Columbus, OH 43210 USA
[2] Ohio State Univ, Dept Pharmacol, Columbus, OH 43210 USA
[3] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Div Human Genet, Columbus, OH 43210 USA
[4] Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
[5] Cleveland Clin Fdn, Genom Med Inst, Cleveland, OH 44195 USA
[6] Cleveland Clin Fdn, Taussig Canc Ctr, Cleveland, OH 44195 USA
关键词
D O I
10.1186/1471-2407-6-278
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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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页数:5
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