Allelic loss at chromosome band 8p21.3‐p22 is associated with progression of hepatocellular carcinoma

Abstract

Human hepatocellular carcinomas (HCC) frequently show loss of heterozygosity at loci on the short arm of chromosome 8. To define a region on 8p commonly deleted in HCC, we used 20 restriction fragment length polymorphism markers to carry out detailed deletion mapping in 142 HCC. Of the 124 informative cases, 56 (45%) showed allelic losses in tumors. While more than half of them had lost alleles at every locus on the short arm, others lost them partially or interstitially. Common deletion of an 8-cM region flanked by cMSR-32 and cC18-245, at 8p21.3-p22, suggested the presence of a tumor suppressor gene(s) in this interval. Correlation between allelic losses on 8p and clinicopathological parameters were examined in the 51 cases for which detailed clinical data were available; allelic losses on 8p were observed in none of five tumors at stage T1 (0%), nine of 20 tumors at stage T2 (45%), and 17 of 26 tumors at stage T3/T4 (65%). A higher frequency of allelic losses on 8p was observed in poorly differentiated tumors (10/14, 71%) than in well differentiated tumors (3/13, 23%). The association of allelic losses on 8p with advanced clinical stage and poor differentiation implies that loss or inactivation of a tumor suppressor gene(s) on 8p may play a role in the progression of HCC.

Identification of three distinct regions of allelic deletions on the short arm of chromosome 8 in hepatocellular carcinoma

“…On the basis of the minimal regions of overlapping deletions on chromosome 8p, we identify three regions possibly containing TSG involved in human liver carcinogenesis. Our data are consistent with previously reported patterns of molecular changes (Emi et al, 1993;Fujiwara et al, 1994;Becker et al, 1996).…”

“…The chromosome segment de®ned in our LOH analysis as MRL2 (D8S261-D8S1790) corresponds to the same region. Furthermore, the MRL2 is totally included in the region of loss de®ned previously for HCC by Emi and coworkers (from locus MSR to locus LPL) (Emi et al, 1993).…”

Chromosomal aberrations in human hepatocellular carcinomas associated with hepatitis C virus infection detected by comparative genomic hybridization

“…Recently p73, whose function is related to p53, was isolated from 1p36 (Kaghad et al, 1997). Unidentified suppressor genes associated with HCC appear to present on chromosome 8p (Emi et al, 1993;Fujiwara et al, 1994). The underrepresentation of 17p (45%) in our study is explained by loss of the p53 gene (17p13.1), a frequent feature of HCC (Fujimoto et al, 1994).…”

Allelic Imbalance of 8p Indicates Poor Survival in Gastric Cancer

“…Chromosome 8p has been found to be altered in other cancers including those arising from the colon, 14 -24 ovary, 21 prostate, [25][26][27][28][29] bladder, 30 lung, 21,31 breast, 32 pancreas, 33 and liver. 21,34 These data support the hypothesis that gene(s) on the p arm of chromosome 8 have an important role in the development and/or progression of tumors from multiple sites.…”