title: Failure to detect genetic alteration of the mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) gene in hepatocellular carcinomas in Japan.
abstract: The mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) suppresses cell growth through binding to the insulin-like growth factor 2 (IGF2) and latent complex of the transforming growth factor-beta (TGF-beta). Recently, it was reported in the United States that loss of heterozygosity (LOH) and mutations in exons 27, 28, and 31 of the M6P/IGF2R gene are frequent in hepatocellular carcinomas (HCCs) and adenomas. In view of the possible importance of this finding, especially for differential diagnosis of small hepatic lesions, we analyzed 43 primary HCCs, 2 adenomatous hyperplasias (AHs), and 3 regenerative nodules (RNs) developing in 42 Japanese patients in Japan for LOH using the polymorphic locus and for mutations by both single strand conformation polymorphism (SSCP) and direct sequencing methods. In the LOH study, 21 out of 22 informative HCCs and all of the informative AHs and RNs showed no allelic loss. In mutational studies of exons 27, 28, and 31, no mutations were detected either by SSCP or direct sequencing analysis in any of the 48 lesions. Thus inactivation of the M6P/IGF2R gene because of genetic alteration does not appear to be essential for hepatocarcinogenesis in Japan.
authors.affiliation: Department of Pathology, The Cancer Institute of Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Wada
authors.forename: H
authors.initials: H
authors.lastname: Kanada
authors.forename: K
authors.initials: K
authors.lastname: Nomura
authors.forename: Y
authors.initials: Y
authors.lastname: Kato
authors.forename: R
authors.initials: R
authors.lastname: Machinami
authors.forename: T
authors.initials: T
authors.lastname: Kitagawa
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000601:surgery; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000601:surgery; D005091:Exons; D006801:Humans; D006965:Hyperplasia; D007438:Introns; D007564:Japan; D008113:Liver Neoplasms / Q000235:genetics* / Q000601:surgery; D019656:Loss of Heterozygosity; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017527:Receptor, IGF Type 2 / Q000235:genetics*; D014481:United States
chemical_list: D017527:Receptor, IGF Type 2