Mapping of Liver Caner Genome: Common Altered Loci and Strategies for Gene Cloning

10.30047/JGMB.200006.0006

Pei-Jer Chen；Shiou-Hwei Yeh；Ming-Yang Lai；Ding-Shinn Chen

Journal of Genetics and Molecular Biology

11卷2期（2000 / 06 / 01）

80 - 80

英文

Liver cancer (hepatocellular carcinoma, HCC) are strongly associated with persistent hepatitis B or C virus infection. Nevertheless, like other cancers, it is caused by multiple genetic mutations in the genomes. Searching for these specific mutations require a genome-wide approach. By loss of heterozygosity and comparative genomic hybridization, common chromosomal amplification are found in 1q, 6q, 8q, 17q and frequent loss in 1p, 4p, 8p, 13q, 16q and 17p. These loci are around 10-20 cM in distance and required to be mapped to a more detail to allow cloning of candidate genes. Initially two conventional methods, by screening known genes mapped in this regions and by sequencing the target loci on chromosome 4q, are taken. A few candidate genes are under testing. T target locus on chromosome 4q have been sequenced up to 10 cM and about 300 genes are being annotated. Interesting genes are to be selected and examined in primary HCC tissues for detecting mutations. We also explored other approaches for narrowing down the locus. YAC included in the target regions are to be transferred back to HCC cell lines to determine a reversion of tumor phenotypes. BAC or cosmid matrix are used to screen for possible homozygous deletion of HCC in the target locus. A correlation between expression of HCC marker, alpha-fetoprotein and putative tumor suppressor gene is also undergoing. Finally, we are collaborating with genetic epidemiologist s for collecting members with familial HCC to look for clues of gene linkage. Hopefully these new approaches help the positional cloning of putative tumor suppressor genes in the commonly deleted loci in the chromosomes of HCC.