Failure to detect genetic alteration of the mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) gene in hepatocellular carcinomas in Japan

The mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) s uppresses tell 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 heterozygosit y (LOH) and mutations in exons 27, 28, and 31 of the M6P/IGF2R gene are fre quent in hepatocellular carcinomas (HCCs) and adenomas. In view of the poss ible importance of this finding, especially for differential diagnosis of s mall hepatic lesions, we analyzed 43 primary HCCs, 2 adenomatous hyperplasi as (AHs), and 3 regenerative nodules (RNs) developing in 42 Japanese patien ts in Japan for LOH using the polymorphic locus and for mutations by both s ingle strand conformation polymorphism (SSCP) and direct sequencing methods . In the Loll study, 21 out of 22 informative HCCs and all of the informati ve AHs and RNs showed no allelic loss, In mutational studies of exons 27, 2 8, and 31, no mutations were detected either by SSCP or direct sequencing a nalysis in any of the 48 lesions. Thus inactivation of the M6P/IGF2R gene b ecause of genetic alteration does not appear to be essential for hepatocarc inogenesis in Japan.