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. 2016 May;29(5):511-5.
doi: 10.1038/modpathol.2016.53. Epub 2016 Mar 11.

High prevalence of TERT promoter mutations in primary squamous cell carcinoma of the urinary bladder

Morgan Cowan  1 , Simeon Springer  2   3 , Doreen Nguyen  1 , Diana Taheri  1 , Gunes Guner  1 , Maria Angelica Mendoza Rodriguez  1 , Yuxuan Wang  3 , Isaac Kinde  3 , Christopher J VandenBussche  1 , Matthew T Olson  1 , Isabela Cunha  4 , Kazutoshi Fujita  5 , Dilek Ertoy  6 , Trinity J Bivalacqua  7 , Kenneth Kinzler  2   3 , Bert Vogelstein  2   3 , George J Netto  1   7 , Nickolas Papadopoulos  2   3
Affiliations

High prevalence of TERT promoter mutations in primary squamous cell carcinoma of the urinary bladder

Morgan Cowan et al. Mod Pathol. 2016 May.

Abstract

TERT promoter mutations (TERT-mut) are detectable in the majority of urothelial carcinomas. The detection of TERT-mut in urine is under investigation as a potential urine-based molecular-screening assay for bladder cancer. A small but significant number of bladder carcinomas are pure squamous cell carcinoma. We sought to assess the incidence of TERT-mut in squamous cell carcinoma of the urinary bladder. A retrospective search of the institutional pathology archives yielded 15 cystectomy specimens performed for squamous cell carcinoma (2000-2014). Histologic slides were reviewed by a senior urologic pathologist to confirm the diagnosis and select a representative formalin-fixed paraffin-embedded tissue block for mutational analysis. All cases yielded adequate material for DNA analysis. Sequencing for TERT-mut was performed using previously described SafeSeq technique. We detected TERT-mut in 12/15 (80%) of bladder squamous cell carcinomas. TERT promoter mutations, commonly found in conventional urothelial carcinoma, are also highly prevalent in urinary bladder squamous cell carcinoma suggesting a common tumorigenesis and potential utility as a molecular urine-based-screening assay.

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Conflict of interest statement

Disclosure/conflict of interest

KWK, NP, and BV are founders of Personal Genome Diagnostics, PapGene, and advise Sysmex-Inostics. These companies and others have licensed technologies from Johns Hopkins, of which BV, KWK, and NP are inventors and receive royalties from these licenses. The terms of these arrangements are being managed by the university in accordance with its conflict of interest policies.

Figures

Figure 1
Figure 1
Two mutational ‘hotspots are repeatedly seen in the TERT promoter, at position 250 anal position228. Both of the mutations are a C-> T base substitution mutation.
See this image and copyright information in PMC

References

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