Implications of a RAD54L polymorphism (2290C/T) in human meningiomas as a risk factor and/or a genetic marker

BMC Cancer. 2003 Mar 4:3:6. doi: 10.1186/1471-2407-3-6. Epub 2003 Mar 4.

Abstract

Background: RAD54L (OMIM 603615, Locus Link 8438) has been proposed as a candidate oncosupressor in tumours bearing a non-random deletion of 1p32, such as breast or colon carcinomas, lymphomas and meningiomas. In a search for RAD54L mutations in 29 menigiomas with allelic deletions in 1p, the only genetic change observed was a silent C/T transition at nucleotide 2290 in exon 18. In this communication the possible association of the 2290C/T polymorphism with the risk of meningiomas was examined. In addition, the usefulness of this polymorphism as a genetic marker within the meningioma consensus deletion region in 1p32 was also verified. The present study comprises 287 blood control samples and 70 meningiomas from Spain and Ecuador. Matched blood samples were only available from Spanish patients.

Results: The frequency of the rare allele-T and heterozygotes for the 2290C/T polymorphism in the blood of Spanish meningioma patients and in the Ecuadorian meningioma tumours was higher than in the control population (P < 0.05). Four other rare variants (2290C/G, 2299C/G, 2313G/A, 2344A/G) were found within 50 bp at the 3' end of RAD54L. Frequent loss of heterozygosity for the 2290C/T SNP in meningiomas allowed to further narrow the 1p32 consensus region of deletion in meningiomas to either 2.08 Mbp - within D1S2713 (44.35 Mbp) and RAD54L (46.43 Mbp) - or to 1.47 Mbp - within RAD54L and D1S2134 (47.90 Mbp) - according to recent gene mapping results.

Conclusion: The statistical analysis of genotypes at the 2290C/T polymorphism suggest an association between the rare T allele and the development of meningeal tumours. This polymorphism can be used as a genetic marker inside the consensus deletion region at 1p32 in meningiomas.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Alleles
  • Biomarkers, Tumor / genetics*
  • Cytosine
  • DNA Helicases
  • DNA Repair / genetics
  • DNA-Binding Proteins
  • Female
  • Gene Frequency / genetics
  • Genetic Carrier Screening
  • Humans
  • Male
  • Meningioma / genetics*
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Polymorphism, Genetic / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors
  • Sex Distribution
  • Spain
  • Thymine

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Cytosine
  • Adenosine Triphosphatases
  • DNA Helicases
  • RAD54L protein, human
  • Thymine