Evaluation of DLC1 as a prostate cancer susceptibility gene: Mutation screen and association study

Siqun L. Zheng, Josyf C. Mychaleckyj, Gregory A. Hawkins, Sarah D. Isaacs, Kathy E. Wiley, Aubrey Turner, Bao Li Chang, Chris Von Kap-Herr, John D. Carpten, Mark Pettenati, Eugene R. Bleecker, Patrick Walsh, Jeffrey M. Trent, Deborah A. Meyers, William B Isaacs, Jianfeng Xu

Research output: Contribution to journalArticle

Abstract

A gene or genes on chromosome 8p22-23 have been implicated in prostate carcinogenesis by the observation of frequent deletions of this region in prostate cancer cells. More recently, two genetic linkage studies in hereditary prostate cancer (HPC) families suggest that germline variation in a gene in this region may influence prostate cancer susceptibility as well. DLC1 (deleted in liver cancer), a gene in this interval, has been proposed as a candidate tumor suppressor gene because of its homology (86% similarity) with rat p122 RhoGAP, which catalyzes the conversion of active GTP-bound rho complex to the inactive GDP-bound form, and thus suppresses Ras-mediated oncogenic transformation. A missense mutation and three intronic insertions/deletions in 126 primary colorectal tumors have been previously identified. However, there are no reports of DLC1 mutation screening in prostate tumors or in germ line DNA of prostate cancer patients. In this study, we report the results of the first mutation screen and association study of DLC1 in genomic DNA samples from hereditary and sporadic prostate cancer patients. The PCR products in the 5′ UTR, all 14 exons, exon-intron junctions, and 3′ UTR were directly sequenced in 159 HPC probands. Eight exonic nucleotide polymorphisms (SNPs) were identified, only one of which resulted in an amino acid change. Twenty-three other SNPs were identified in intronic regions. Seven informative SNPs that spanned the complete DLC1 gene were genotyped in an additional 249 sporadic cases and 222 unaffected controls. No significant difference in the allele and genotype frequencies were observed among HPC probands, sporadic cases, and unaffected controls. These results suggest that DLC1 is unlikely to play an important role in prostate cancer susceptibility.

Original languageEnglish (US)
Pages (from-to)45-53
Number of pages9
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume528
Issue number1-2
DOIs
StatePublished - Jul 25 2003

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Neoplasm Genes
Prostatic Neoplasms
Single Nucleotide Polymorphism
Mutation
Genes
Prostate
Exons
Genetic Linkage
5' Untranslated Regions
DNA
3' Untranslated Regions
Missense Mutation
Liver Neoplasms
Guanosine Triphosphate
Tumor Suppressor Genes
Gene Frequency
Germ Cells
Introns
Colorectal Neoplasms
Carcinogenesis

Keywords

  • Association
  • DLC1
  • Hereditary
  • Mutation screen
  • Prostate cancer
  • SNPs

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

Cite this

Evaluation of DLC1 as a prostate cancer susceptibility gene : Mutation screen and association study. / Zheng, Siqun L.; Mychaleckyj, Josyf C.; Hawkins, Gregory A.; Isaacs, Sarah D.; Wiley, Kathy E.; Turner, Aubrey; Chang, Bao Li; Von Kap-Herr, Chris; Carpten, John D.; Pettenati, Mark; Bleecker, Eugene R.; Walsh, Patrick; Trent, Jeffrey M.; Meyers, Deborah A.; Isaacs, William B; Xu, Jianfeng.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 528, No. 1-2, 25.07.2003, p. 45-53.

Research output: Contribution to journalArticle

Zheng, SL, Mychaleckyj, JC, Hawkins, GA, Isaacs, SD, Wiley, KE, Turner, A, Chang, BL, Von Kap-Herr, C, Carpten, JD, Pettenati, M, Bleecker, ER, Walsh, P, Trent, JM, Meyers, DA, Isaacs, WB & Xu, J 2003, 'Evaluation of DLC1 as a prostate cancer susceptibility gene: Mutation screen and association study', Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, vol. 528, no. 1-2, pp. 45-53. https://doi.org/10.1016/S0027-5107(03)00081-2
Zheng, Siqun L. ; Mychaleckyj, Josyf C. ; Hawkins, Gregory A. ; Isaacs, Sarah D. ; Wiley, Kathy E. ; Turner, Aubrey ; Chang, Bao Li ; Von Kap-Herr, Chris ; Carpten, John D. ; Pettenati, Mark ; Bleecker, Eugene R. ; Walsh, Patrick ; Trent, Jeffrey M. ; Meyers, Deborah A. ; Isaacs, William B ; Xu, Jianfeng. / Evaluation of DLC1 as a prostate cancer susceptibility gene : Mutation screen and association study. In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 2003 ; Vol. 528, No. 1-2. pp. 45-53.
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abstract = "A gene or genes on chromosome 8p22-23 have been implicated in prostate carcinogenesis by the observation of frequent deletions of this region in prostate cancer cells. More recently, two genetic linkage studies in hereditary prostate cancer (HPC) families suggest that germline variation in a gene in this region may influence prostate cancer susceptibility as well. DLC1 (deleted in liver cancer), a gene in this interval, has been proposed as a candidate tumor suppressor gene because of its homology (86{\%} similarity) with rat p122 RhoGAP, which catalyzes the conversion of active GTP-bound rho complex to the inactive GDP-bound form, and thus suppresses Ras-mediated oncogenic transformation. A missense mutation and three intronic insertions/deletions in 126 primary colorectal tumors have been previously identified. However, there are no reports of DLC1 mutation screening in prostate tumors or in germ line DNA of prostate cancer patients. In this study, we report the results of the first mutation screen and association study of DLC1 in genomic DNA samples from hereditary and sporadic prostate cancer patients. The PCR products in the 5′ UTR, all 14 exons, exon-intron junctions, and 3′ UTR were directly sequenced in 159 HPC probands. Eight exonic nucleotide polymorphisms (SNPs) were identified, only one of which resulted in an amino acid change. Twenty-three other SNPs were identified in intronic regions. Seven informative SNPs that spanned the complete DLC1 gene were genotyped in an additional 249 sporadic cases and 222 unaffected controls. No significant difference in the allele and genotype frequencies were observed among HPC probands, sporadic cases, and unaffected controls. These results suggest that DLC1 is unlikely to play an important role in prostate cancer susceptibility.",
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AU - Von Kap-Herr, Chris

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