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Background  Genome wide association studies (GWAS) have identified several genetic variants that are associated with prostate cancer. Most of these variants, like other GWAS association signals, are located in non-coding regions of potential candidate genes, and thus could act at the level of the mRNA transcript.    Methods  We measured the expression and isoform usage of seven prostate cancer candidate genes in benign and malignant prostate by real-time PCR, and correlated these factors with cancer status and genotype at the GWAS risk variants.    Results  We determined that levels of  LMTK2  transcripts in prostate adenocarcinomas were only 32% of those in benign tissues (p = 3.2 × 10 -7 ), and that an independent effect of genotype at variant rs6465657 on  LMTK2  expression in benign (n = 39) and malignant tissues (n = 21) was also evident (P = 0.002). We also identified that whilst  HNF1B(C)  and  MSMB2  comprised the predominant isoforms in benign tissues (90% and 98% of total  HNF1B  or  MSMB  expression) , HNF1B(B) and MSMB1  were predominant in malignant tissue (95% and 96% of total  HNF1B  or  MSMB  expression; P = 1.7 × 10 -7  and 4 × 10 -4  respectively), indicating major shifts in isoform usage.    Conclusions  Our results indicate that the amount or nature of mRNA transcripts expressed from the  LMTK2 ,  HNF1B  and  MSMB  candidate genes is altered in prostate cancer, and provides further evidence for a role for these genes in this disorder. The alterations in isoform usage we detect highlights the potential importance of alternative mRNA processing and moderation of mRNA stability as potentially important disease mechanisms.

Alterations in LMTK2, MSMB and HNF1B gene expression are associated with the development of prostate cancer