Genetic changes and expression of the mannose 6-phosphate/insulin-like growth factor II receptor gene in human hepatitis B virus-associated hepatocellular carcinoma.
It was reported that 60-70% of hepatitis B virus (HBV)-negative hepatocellular carcinoma (HCC) had loss of heterozygosity (LOH) at the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) locus and this gene was mutated in 55% of these patients with LOH. In this study, genomic DNA from 29 pairs of HBV-positive HCC and corresponding non-tumor tissues was used to analyze LOH at the M6P/IGF2R locus and single deoxyguanosine deletion in this gene by PCR. Total RNA from 19 of the 29 patients was utilized to determine a 192 bp insert in the M6P/IGF2R mRNA and expression of this gene by RT-PCR. Twenty-eight of 29 (97%) HBV-positive HCC were found to be informative at the M6P/IGF2R locus but LOH at this region was only detected in 4/28 (14%) informative patients. Neither single deoxyguanosine deletion in this gene nor 192 bp insert in its mRNA occurred in these patients. Compared with corresponding non-tumor tissues, expression of the M6P/IGF2R mRNA was decreased in 13/19 (68%) HBV-positive HCC tissues, suggesting that M6P/IGF2R may be involved in HBV-associated hepatocarcinogenesis by the regulation of its expression level. In the development of HBV-associated HCC, M6P/IGF2R mutation may not be a major agent.
Department of Experimental Surgery, Singapore General Hospital, Singapore 169608. gesyeb@sgh.com.sg
Er-Bin
EB
Yang
Liu-Liang
LL
Qin
Yin-Nong
YN
Zhao
Kai
K
Zhang
Pierce
P
Chow
D000328:Adult; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006509:Hepatitis B / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000235:genetics*
D018076:DNA, Complementary; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017527:Receptor, IGF Type 2