Mutational analysis of SPANX genes in families with X-linked prostate cancer.
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.
Kouprina
Natalay
N
Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, Maryland, USA. kouprinn@mail.nih.gov
Noskov
Vladimir N
VN
Solomon
Greg
G
Otstot
John
J
Isaacs
William
W
Xu
Jianfeng
J
Schleutker
Johanna
J
Larionov
Vladimir
V
D041321:Chromosomes, Human, X / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D004273:DNA, Neoplasm; D009687:Nuclear Proteins; C414403:SPANXA1 protein, human; C521014:SPANXA2 protein, human; C521016:SPANXD protein, human