Sequence variants of DLC1 in colorectal and ovarian tumours

Peter J. Wilson, Edwina McGlinn, Anna Marsh, Tim Evans, Jeremy Arnold, Kim Wright, Kelli Biden, Joanne Young, Brandon Wainwright, Carol Wicking, Georgia Chenevix-Trench

Research output: Contribution to journalArticleResearchpeer-review

32 Citations (Scopus)

Abstract

Loss of heterozygosity occurs frequently on the short arm of chromosome 8 in many neoplasms, including colorectal and ovarian cancer. Monochromosome transfer experiments into colorectal tumour cell lines have provided functional evidence for a tumour suppressor gene located at 8p22-23. One of the genes from this region that is expressed by our suppressed hybrids is a candidate tumour suppressor gene, DLC1 (deleted in liver cancer), which has homology to rat RhoGAP. We have delineated the structure of the DLC1 gene and used single-stranded conformation polymorphism analysis (SSCP) to look for sequence variants in 126 colorectal and 33 ovarian primary tumours and cell lines. One exonic missense mutation and three intronic insertions/deletions were identified in primary colorectal tumours, as well as many polymorphisms present in germline DNAs. The rarity of exonic missense mutations, and the absence of protein-truncating mutations, indicates that DLC1 is not the target of 8p LOH in colorectal or ovarian tumours. The delineation of the gene structure allows mutation analysis of DLC1 in other tumour types for which it remains a candidate tumour suppressor gene based on its location and homology to rhoGAP. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)156-165
Number of pages10
JournalHuman Mutation
Volume15
Issue number2
DOIs
Publication statusPublished - 2000
Externally publishedYes

Keywords

  • Colorectal cancer
  • DLC1
  • Ovarian cancer
  • Tumour suppressor gene

Cite this