title: A novel mutation in the tyrosine kinase domain of ERBB2 in hepatocellular carcinoma.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA. Tanios.Bekaii-Saab@osumc.edu
authors.forename: Tanios
authors.initials: T
authors.lastname: Bekaii-Saab
authors.forename: Nita
authors.initials: N
authors.lastname: Williams
authors.forename: Christoph
authors.initials: C
authors.lastname: Plass
authors.forename: Miguel Villalona
authors.initials: MV
authors.lastname: Calero
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics*; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D011505:Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases