Somatic mutations of the <i>ERBB4</i> kinase domain in human cancers

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P><P>The EGFR family consists of 4 receptor tyrosine kinases, EGFR (ERBB1), ERBB2 (HER2), ERBB3 (HER3) and ERBB4 (HER4). Recent reports revealed that the kinase domains of both <I>EGFR</I> (<I>ERBB1</I>) and <I>ERBB2</I> gene were somatically mutated in human cancers, raising the possibility that the other ERBB members possess somatic mutations in human cancers. Here, we performed mutational analysis of the <I>ERBB4</I> kinase domain by polymerase chain reaction–single‐strand conformation polymorphism assay in 595 cancer tissues from stomach, lung, colon and breast. We detected the <I>ERBB4</I> somatic mutations in 3 of 180 gastric carcinomas (1.7%), 3 of 104 colorectal carcinomas (2.9%), 5 of 217 nonsmall cell lung cancers (2.3%) and 1 of 94 breast carcinomas (1.1%). The 12 <I>ERBB4</I> mutations consisted of 1 in‐frame duplication mutation and 8 missense mutations in the exons, and 3 mutations in the introns. We simultaneously analyzed the somatic mutations of <I>EGFR</I>, <I>ERBB2, K‐RAS</I>, <I>PIK3CA</I> and <I>BRAF</I> genes in the 12 samples with the <I>ERBB4</I> mutations and found that 1 gastric carcinoma with <I>ERBB4</I> mutation also harbored <I>K‐RAS</I> gene mutation. Our study demonstrated that in addition to <I>EGFR</I> and <I>ERBB2</I>, somatic mutation of the kinase domain of <I>ERBB4</I> occurs in the common human cancers, and suggested that alterations of ERBB4‐mediated signaling pathway by <I>ERBB4</I> mutations may contribute to the development of human cancers. © 2005 Wiley‐Liss, Inc.</P>