Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in hepatocellular carcinoma.

Abstract

Loss of heterozygosity of chromosome 10q has been reported in hepatoma. Areas with a high rate of loss of genetic material could harbor putative tumor suppressor genes. PTEN/MMAC1, a candidate tumor suppressor gene located at chromosome 10q23.3, has recently been identified and found to be homozygously deleted or mutated in several different types of human tumors. To determine whether the PTEN/MMAC1 gene is a target of 10q loss of heterozygosity in hepatoma, we examined 42 primary hepatomas for mutations in PTEN/MMAC1 by using nested reverse transcriptase polymerase chain reaction (RT-PCR) of the RNA and single-stranded conformation polymorphism (SSCP) analysis of all genomic exons. Although 2 of 42 hepatoma tissues had aberrant transcripts, 5 matched noncancerous liver tissues also had aberrant transcripts. Southern blot analysis of the entire genomic DNA revealed no genomic change. Therefore, like the TSG101 or FHIT gene, aberrant transcripts of PTEN/MMAC1 using the nested RT-PCR method were a common phenomenon for both cancerous and noncancerous liver tissues, which may not be related to oncogenesis. None of the 42 cases had small deletions, point mutations, or insertions. Our results suggest that the PTEN/MMAC1 gene may not play a role in the pathogenesis of hepatoma.

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