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ABSTRACT: Context
Among the genomic loci harboring potential candidate genes for prostatic cancer (PCa) is the 2q31-33 chromosomal region that harbors the gene encoding phosphodiesterase 11A (PDE11A). In addition, the combined cancer genome expression metaanalysis datasets included PDE11A among the top 1% down-regulated genes in PCa.Objective
In the present study, we screened 50 unrelated PCa patients of Brazilian descent for PDE11A coding defects.Design
The study consisted of PDE11A sequencing, in vitro functional assays, and immunostaining analysis.Results
We identified eight different sequence alterations in 15 patients (30%): one stop-codon and seven missense mutations. Three of the variants (R202C, Y658C, and E840K) were novel, and the remaining five (Y727C, R804H, R867G, M878V, and R307X) have been associated with predisposition to adrenal or testicular tumors. The overall prevalence of PDE11A-inactivating sequence variants among PCa patients was significantly higher than in 287 healthy controls (0.16 vs. 0.051, respectively, P < 0.001, odds ratio 3.81, 95% confidence interval 1.86-7.81) and the R202C, Y658C, and E840K substitutions were not found in controls. All missense mutations led to decreased PDE11A activity in human embryonic kidney 293 and PC3M cells and immunostaining of PCa samples with sequence changes showed decreased PDE11A protein expression.Conclusion
Our data suggest that, like in the adrenal cortex and the testicular germ cells, PDE11A-inactivating genetic alterations may play a role in susceptibility to PCa.
SUBMITTER: Faucz FR
PROVIDER: S-EPMC3038491 | biostudies-literature | 2011 Jan
REPOSITORIES: biostudies-literature
Faucz Fabio Rueda FR Horvath Anelia A Rothenbuhler Anya A Almeida Madson Q MQ Libé Rossella R Raffin-Sanson Marie-Laure ML Bertherat Jerome J Carraro Dirce Maria DM Soares Fernando Augusto FA Soares Fernando Augusto FA Molina Gustavo de Campos Gde C Campos Antonio H AH Alexandre Rodrigo B RB Bendhack Marcelo Luiz ML Nesterova Maria M Stratakis Constantine A CA
The Journal of clinical endocrinology and metabolism 20100929 1
<h4>Context</h4>Among the genomic loci harboring potential candidate genes for prostatic cancer (PCa) is the 2q31-33 chromosomal region that harbors the gene encoding phosphodiesterase 11A (PDE11A). In addition, the combined cancer genome expression metaanalysis datasets included PDE11A among the top 1% down-regulated genes in PCa.<h4>Objective</h4>In the present study, we screened 50 unrelated PCa patients of Brazilian descent for PDE11A coding defects.<h4>Design</h4>The study consisted of PDE1 ...[more]