ERBB3 kinase domain mutations are rare in lung, breast and colon carcinomas.

摘要

Dear Sir,Protein tyrosine kinases, which regulate cell signaling pathways mediating a number of processes in cell survival and growth, comprise a large fraction of the dominant oncogenes known to date. The EGFR family consisted of 4 receptor tyrosine kinases, EGFR (ERBB1/ HER1), ERBB2 (HER2), ERBB3 (HER3) and ERBB4 (HER4).1Recent studies demonstrated that lung adenocarcinomas possessed EGFR gene mutations, which could predict significant clinical responses to gefitinib (Iressa) and erlotinib (Tar-ceva), the orally active EGFR tyrosine kinase inhibitors.2 ERBB2 overexpression by the ERBB2gene amplification is present in ~25% of invasive breast cancers, and the humanized antibody trastuzumab (Herceptin) against the overexpressed ERBB2 is proven to be effective in treating breast cancers with ERBB2 amplification. In addition, the ERBB2 kinase domain mutations have been detected in lung, gastric, colorectal and breast carcinomas.4"5 The kinase domain mutations of ERBB4 have also been detected in lung, gastric, colorectal and breast carcinomas. These data indicate that the kinase domains of the ERBB family are common targets of genetic alterations in human cancers.