DNA variants of DLC-1, a candidate tumor suppressor gene in human hepatocellular carcinoma

  • Authors:
    • Sang-Won Park
    • Marian E. Durkin
    • Snorri S. Thorgeirsson
    • Nicholas C. Popescu
  • View Affiliations

  • Published online on: July 1, 2003     https://doi.org/10.3892/ijo.23.1.133
  • Pages: 133-137
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Abstract

The DLC-1 gene encoding a regulator of the Rho family of small GTPases is altered in breast, prostate, colon, and liver cancer and has several characteristics of a tumor suppressor gene. DLC-1 overexpression causes inhibition of in vitro growth of liver tumor cells and complete suppression of in vivo tumorigenicity of breast tumor cells. Inactivation and aberrant expression of DLC-1 in human hepatocellular carcinoma (HCC) is frequently associated with hemizygous and homozygous genomic deletion and promoter methylation. Since inactivation of tumor suppressor genes in cancer cells is also commonly associated with point mutation, we evaluated the incidence of mutation of the DLC-1 gene by PCR-SSCP in 17 primary HCC and 18 HCC cell lines. One missense mutation was detected at codon 991 of exon 12 (C↷T transition, Val↷Ile) in an HCC cell line. In addition, two types of polymorphisms were identified: a G↷T at codon 745 of exon 9, a T↷C at 17 bp downstream of exon 2. While the pathogenic relevance of the intronic polymorphism is not known, the low rate of mutation of the DLC-1 gene in HCC implies that genomic deletion and promoter methylation primarily account for the altered expression and tumor suppressive inactivation of the DLC-1 gene.

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July 2003
Volume 23 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Park, S., Durkin, M.E., Thorgeirsson, S.S., & Popescu, N.C. (2003). DNA variants of DLC-1, a candidate tumor suppressor gene in human hepatocellular carcinoma. International Journal of Oncology, 23, 133-137. https://doi.org/10.3892/ijo.23.1.133
MLA
Park, S., Durkin, M. E., Thorgeirsson, S. S., Popescu, N. C."DNA variants of DLC-1, a candidate tumor suppressor gene in human hepatocellular carcinoma". International Journal of Oncology 23.1 (2003): 133-137.
Chicago
Park, S., Durkin, M. E., Thorgeirsson, S. S., Popescu, N. C."DNA variants of DLC-1, a candidate tumor suppressor gene in human hepatocellular carcinoma". International Journal of Oncology 23, no. 1 (2003): 133-137. https://doi.org/10.3892/ijo.23.1.133