TY - JOUR
T1 - A novel mutation in the tyrosine kinase domain of ERBB2 in hepatocellular carcinoma
AU - Bekaii-Saab, Tanios
AU - Williams, Nita
AU - Plass, Christoph
AU - Calero, Miguel Villalona
AU - Eng, Charis
PY - 2006/12/6
Y1 - 2006/12/6
N2 - 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.
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.
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U2 - 10.1186/1471-2407-6-278
DO - 10.1186/1471-2407-6-278
M3 - Article
C2 - 17150109
AN - SCOPUS:33845874148
SN - 1471-2407
VL - 6
JO - BMC cancer
JF - BMC cancer
M1 - 278
ER -