Mutational analysis of SPANX genes in families with X-linked prostate cancer

Prostate. 2007 Jun 1;67(8):820-8. doi: 10.1002/pros.20561.

Abstract

Background: Previous genetic linkage studies identified a locus for susceptibility to prostate cancer called HPCX at Xq27. The candidate region contains two clusters of SPANX genes. The first cluster called SPANX-A/D includes SPANX-A1, SPANX-A2, SPANX-B, SPANX-C, and SPANX-D; the second cluster called SPANX-N includes SPANX-N1, SPANX-N2, SPANX-N3, and SPANX-N4. The SPANX genes encode cancer-testis (CT) specific antigens. Previous studies identified SPANX-B and SPANX-D variants produced by gene conversion events, none of which are associated with X-linked prostate cancer.

Methods: In this study we applied transformation-associated recombination cloning (TAR) in yeast to analyze sequence variations in SPANX-A1, SPANX-A2, and SPANX-C genes that are resided within large chromosomal duplications. A SPANX-N1/N4 cluster was analyzed by a routine PCR analysis.

Results: None of the sequence variations in the coding regions of these genes is associated with susceptibility to prostate cancer.

Conclusions: Therefore, genetic variation in the SPANX genes is not the actual target variants explaining HPCX. However, it is possible that they play a modifying role in susceptibility to prostate cancer through complex recombinational interaction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human, X / genetics*
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Humans
  • Male
  • Nuclear Proteins / genetics*
  • Point Mutation
  • Polymerase Chain Reaction
  • Prostatic Neoplasms / genetics*
  • Sequence Alignment
  • Sequence Analysis, DNA

Substances

  • DNA, Neoplasm
  • Nuclear Proteins
  • SPANXA1 protein, human
  • SPANXA2 protein, human
  • SPANXD protein, human