Frequency of <b><i>TERT</i></b> Promoter Mutations in Prostate Cancer

Abstract

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 has been associated with a poor prognosis and higher risk for disease recurrence. The underlying mechanisms for high TERT expression in PrCa have still not been clarified. 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 microdissected and used for DNA isolation. The mutation hotspot region within the TERT core promoter (-260 to +60) was analyzed by direct Sanger sequencing or SNaPshot analysis. Results: All cases were analyzed successfully. Mutations within the core promoter of the TERT gene were not detected in any of the cases with all tumors exhibiting a wild-type sequence. Conclusion:TERT core promoter mutations reported from several other malignancies were not detected in our unselected cohort of PrCa. These data indicate that alterations within the core promoter of the TERT gene do not play an important role in prostate carcinogenesis.

Telomerase reverse transcriptase (TERT) promoter mutations are rare in urachal cancer

“…21 In addition, TERT promoter mutations have been detected in (inverted) papilloma 22,23 and papillary urothelial neoplasm of low malignant potential (PUNLMP), 23 while no mutations have been observed in benign lesions/changes of the bladder. 12,14,19,22 These facts together with low rates of TERT promoter mutations in renal cell carcinomas 9 and absence in prostate cancer 9,14,24 and the feasibility of detection in urine sample, led to the suggestion that TERT promoter mutation analysis of urine samples might be used for the disease monitoring of (non-invasive) UC. 11,12 In contrast to UC, TERT promoter mutations have not been detected in colorectal adenocarcinomas and conflicting results have been reported in primary bladder adenocarcinomas (PBAC).…”

The Microphthalmia-Associated Transcription Factor p.E318K Mutation Does Not Play a Major Role in Sporadic Renal Cell Tumors from Caucasian Patients

“…DNA was extracted from renal tumor samples from serial sections after manual microdissection as described previously [13]. In brief, 5-µm-thick serial sections of the tumor tissue were dewaxed and stained with 0.1% methylene blue for 15 s. Using an inverted microscope, the tumor tissue (identified through matching with a marked hematoxylin and eosin-stained section reviewed by an experienced surgical pathologist) was scraped off with a sterile needle to obtain a purity of the cells of at least 85%.…”

Telomeres and telomerase in prostate cancer development and therapy

“…Two well-documented mechanisms are hypermethylation of the TERT promoter, which has been reported in multiple cancer cell lines 137 , and activating point mutations in the TERT promoter, which have been observed in cancers of the central nervous system, bladder, thyroid, and skin 138,139 . The methylation status of the TERT promoter in prostate cancer has yet to be fully investigated; however, TERT promoter mutations have not been observed in prostate cancer 138,140 . Instead , the MYC oncogene has been implicated as a contributor to TERT overexpression in prostate cancer.…”