Molecular genetic evidence supporting a novel human hepatocellular carcinoma tumor suppressor locus at 13q12.11
Journal
Genes Chromosomes and Cancer
Journal Volume
44
Journal Issue
3
Pages
320-328
Date Issued
2005
Author(s)
Abstract
A novel 1-cM (1.8 Mb) homozygous deletion (HD) on 13q12.11 was identified in a human hepatocellular carcinoma (HCC) cell line, SK-Hep-1, after high-density genetic marker scan and Southern blotting analysis. A loss of heterozygosity (LOH) analysis indicated that LOH frequency of the HD region in 48 pairs of HCC tissues was 52%. Interestingly, the occurrence of LOH in the 13q12.11 HD region is significantly associated with early-onset HCC, inferred from Fisher's exact test (P = 0.0047) and Mann-Whitney test (P = 0.023). Since the novel 1-cM (1.8 Mb) HD region is gene-rich with more than 37 predicted transcripts, we used a candidate gene approach by examining down-regulation of known tumor suppressor genes (TSGs), including LATS2, TG737, CRYL1, and GJB2, in HCC tissues. We detected only 14% down-regulation of the LAST2 gene that flanks the outside of the HD, in HCC tissues, by quantitative RT-PCR assays. However, we observed significant down-regulation of the TG737, CRYL1, and GJB2 genes located within the HD in 59, 64, and 71% of HCC tissues, respectively. Together, our results indicated that the identified 13q12.11 HD region contained at least three significant down-regulated TSGs, and preferential LOH in early-onset HCC patients is a putative tumor suppressor locus in HCC. ? 2005 Wiley-Liss, Inc.
SDGs
Other Subjects
adult; aged; article; cancer cell culture; chromosome 13q; chromosome deletion; CRYL1 gene; down regulation; female; gene locus; genetic marker; GJB2 gene; heterozygosity loss; homozygosity; human; human cell; human tissue; LATS2 gene; liver cell carcinoma; male; molecular genetics; priority journal; quantitative analysis; rank sum test; reverse transcription polymerase chain reaction; Southern blotting; TG737 gene; tumor suppressor gene
Publisher
Wiley-Liss Inc.
Type
journal article