Frequency of TERT promoter mutations in prostate cancer

Objective: Recently, recurrent mutations within the core promoter of the human telomerase reverse transcriptase (TERT) gene generating consensus binding sites for ETS transcription factor family members were described in melanomas and other malignancies (e.g. bladder cancer, hepatocellular carcinoma). These mutations were discussed as early drivers for malignant transformation.

In prostate cancer (PrCa) TERT expression was associated with a poor prognosis and a higher risk for biochemical recurrence. The underlying mechanisms for high TERT expression in PrCa are still not clarified in detail. To date, data on TERT promoter mutation analysis in PrCa are sparse. Therefore, we performed sequence analysis of the core promoter region of the TERT gene in an unselected cohort of prostate tumors.

Methods: Sections from 167 formalin-fixed, paraffin-embedded and cryopreserved prostate tumors were used for DNA isolation. After precise microdissection the mutation hotspot region within the TERT core promoter (-260 to +60) was analysed by direct Sanger sequencing or SNaPshot analysis.

Results: All cases could be analysed successfully. Mutations within the core promoter of the TERT gene could not be detected in any of the cases. All tumors showed wildtype sequence.

Conclusion: TERT core promoter mutations reported from several other malignancies could not be detected in our unselected cohort of prostate cancers. These data indicate that alterations within the core promoter of the TERT gene play no important role in prostate carcinogenesis.