Loss of heterozygosity of the mannose 6-phosphate/insulin-like growth factor II receptor and p53 genes in human hepatocellular carcinoma

Information about M6P/IGF2R and p53 genes in hepatocarcinogenesis is limite d and controversial. We tested the loss of heterozygosity (LOH) of M6P/IGF2 R and p53 genes in cirrhotic and neoplastic foci in surgically resected liv ers of 30 patients with hepatocellular carcinoma (HCC). The DNAs extracted from microdissected specimens were used for polymerase-chain-reaction (PCR) -based assay. LOH of the M6P/IGF2R gene in the primary HCCs was detected in 10 of 22 informative cases (45%). In five of these 10 cases (50%), LOH was detected in cirrhotic lesions adjacent to the HCCs. The allelic loss patte rns of M6P/IGF2R in liver cirrhosis (LC) were identical to those in the cor responding HCC, suggesting that HCC could develop from one of the cells in which M6P/IGF2R had been lost. Furthermore, LOH of the p53 gene in HCC was detected in 10 (43%) of 23 informative cases, and p53 loss in cirrhotic foc i adjacent to HCC was shown in one of the 10 cases (10%). The pattern of al lelic loss of the p53 gene in the cirrhotic foci was identical with that in the corresponding tumor. The LOH of the M6P/IGF2R and p53 genes occurred i ndependently in HCCs. LOH of the M6P/IGF2R locus was a relatively frequent and possibly early event in hepatocarcinogenesis, and LOH of the M6P/IGF2R gene and LOH of the p53 gene occurred independently. (C) 2001 Elsevier Scie nce Ireland Ltd. All rights reserved.