PTEN/MMAC1 Mutation and Frequent Loss of Heterozygosity Identified in Chromosome 10q in a Subset of Hepatocellular Carcinomas

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Abstract
Frequent allelic losses on chromosome 10q have been reported in several types of cancers, suggesting the presence of a putative tumor suppressor gene(s) on the chromosomal arm. We examined loss of heterozygosity (LOH) on chromosome 10q in 37 hepatocellular carcinomas (HCC) using eleven dinucleotide microsatellite markers, spanning the entire chromosome arm of 10q. Twelve (32%) out of 37 informative cases showed allelic losses of at least one locus on 10q and eight tumors showed a partial deletion of 10q. Analysis of deletion mapping of these eight cases identified two commonly deleted regions within the distal part of 10q (10q24‐q26), a 20‐cM interval flanked by D10S597 and D10S216 and a 24‐cM interval flanked by D10S216 and D10S590. Moreover, we detected a somatic missense mutation (Met→Val) of a candidate tumor suppressor gene PTEN/MMAC1, located at 10q23.3, in one HCC with LOH of 10q. Our findings indicated the presence of putative tumor suppressor gene(s) in the distal region of 10q that might be involved in the development and progression of HCC. Inactivation of PTEN/MMAC1 gene located outside the commonly deleted region of 10q might also play an important role in a subset of HCCs.