title: Somatic mutations of the ERBB4 kinase domain in human cancers.
abstract: 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 EGFR (ERBB1) and ERBB2 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 ERBB4 kinase domain by polymerase chain reaction-single-strand conformation polymorphism assay in 595 cancer tissues from stomach, lung, colon and breast. We detected the ERBB4 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 ERBB4 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 EGFR, ERBB2, K-RAS, PIK3CA and BRAF genes in the 12 samples with the ERBB4 mutations and found that 1 gastric carcinoma with ERBB4 mutation also harbored K-RAS gene mutation. Our study demonstrated that in addition to EGFR and ERBB2, somatic mutation of the kinase domain of ERBB4 occurs in the common human cancers, and suggested that alterations of ERBB4-mediated signaling pathway by ERBB4 mutations may contribute to the development of human cancers.
authors.affiliation: Department of Pathology, College of Medicine, Catholic University of Korea, Seoul 137-701, Korea.
authors.forename: Young Hwa
authors.initials: YH
authors.lastname: Soung
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Lee
authors.forename: Su Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Young Pil
authors.initials: YP
authors.lastname: Wang
authors.forename: Keon Hyun
authors.initials: KH
authors.lastname: Jo
authors.forename: Seok Whan
authors.initials: SW
authors.lastname: Moon
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Park
authors.forename: Suk Woo
authors.initials: SW
authors.lastname: Nam
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Nam Jin
authors.initials: NJ
authors.lastname: Yoo
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D066247:Receptor, ErbB-4; D017384:Sequence Deletion
chemical_list: C587689:ERBB4 protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D066247:Receptor, ErbB-4