ID4 is frequently downregulated and partially hypermethylated in prostate cancer.

PURPOSE

The candidate tumor suppressor ID4 is downregulated in various cancers by DNA hypermethylation. We have performed the first systematic analysis of ID4 expression and methylation in prostate cancer.

METHODS

ID4 mRNA expression was analyzed by quantitative RT-PCR in 47 carcinoma and 13 benign prostatic tissues obtained by prostatectomy. Methylation was analyzed in an extended series of samples by methylation-specific MS-PCR and pyrosequencing, controlled by bisulfite sequencing.

RESULTS

ID4 expression was significantly decreased in prostate cancers, especially in cases with adverse clinical and histopathological features and earlier recurrence. Hypermethylation in carcinomas was detected by MS-PCR and pyrosequencing, but the results of the two techniques were not fully concordant. The difference was created by generally partial and heterogeneous methylation. Weak methylation was also detected in benign prostatic tissue samples.

CONCLUSIONS

ID4 downregulation may contribute to prostate cancer pathogenesis and is often accompanied by DNA hypermethylation. The case of ID4 illustrates exemplarily the limits and pitfalls of techniques for the detection of methylation changes in prostate cancer tissues.