Lack of somatic ErbB2 tyrosine kinase domain mutations in hepatocellular carcinoma

Aim: Small molecules targeting the epidermal growth factor receptor (EGFR) intracellular tyrosine kinase domain have shown promising activity in cancer therapeutics. Recent reports suggest activity of erlotinib, an ErbB1 inhibitor, and lapatinib, a dual inhibitor of ErbB1 and ErbB2, in hepatocellular carcinoma (HCC). Activating ErbB1 somatic mutations may predict treatment responses. Method and Results: We have previously reported ErbB1 tyrosine kinase domain mutations to be rare or absent in HCC, but data on the frequency of ErbB2 tyrosine kinase domain mutations in HCC is currently limited, apart from reports of a missense mutation identified in 11% of a small Caucasian sample. We studied exons 18-23 of the ErbB2 gene from tumor DNA of 100 Asian human HCC and found no exonic mutations of potential significance. Conclusion: Alternative mechanisms may be responsible for the observed therapeutic efficacy of ErbB1 and ErbB2 tyrosine kinase inhibitors.