Frequent genetic alterations at the distal region of chromosome 1p in human hepatocellular carcinomas.

Cytogenetic analysis of hepatocellular carcinoma (HCC) cell lines and primary HCC tissues has demonstrated chromosome 1p to be the region most commonly affected. To refine the altered locus, genetic abnormalities of this region were surveyed systemically by microsatellite polymorphism analysis. Twelve sets of primers evenly distributed on chromosome 1p which can amplify di- or tetranucleotide repeat length polymorphism by polymerase chain reaction were selected. The results were then supplemented by the conventional restriction fragment length polymorphism study. A comparison of the allele patterns between 30 pairs of HCC and their corresponding nontumor DNAs discovered chromosome 1p aberrations in 15 of 30 tumors (50%). The abnormalities can be classified into three groups. The first aberration was typical loss of heterozygosity that was found in 9 HCCs (30%). The second aberration was a 2-3-fold increase of allelic dosage, which was detected in 6 HCCs (20%). The third aberration was the novel microsatellite polymorphism, which was detected in 3 cases (10%). These abnormalities seemed to cluster at the distal part of chromosome 1p, with a common region mapped to 1p35-36, which is also the region with frequent loss of heterozygosity in neuroblastoma and colorectal and breast cancers. Therefore, loss of putative tumor suppressor gene(s) in this locus may participate in the development of hepatocellular carcinoma and a wide range of human cancers.