title: High prevalence of TERT promoter mutations in primary squamous cell carcinoma of the urinary bladder.
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.
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Morgan
authors.initials: M
authors.lastname: Cowan
authors.affiliation: Department of Oncology, Johns Hopkins University, Baltimore, MD, USA.|The Ludwig Center for Cancer Genetics and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
authors.forename: Simeon
authors.initials: S
authors.lastname: Springer
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Doreen
authors.initials: D
authors.lastname: Nguyen
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Taheri
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Gunes
authors.initials: G
authors.lastname: Guner
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Maria Angelica Mendoza
authors.initials: MA
authors.lastname: Rodriguez
authors.affiliation: The Ludwig Center for Cancer Genetics and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Ludwig Center for Cancer Genetics and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Kinde
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Christopher J
authors.identifier: 0000-0002-8822-5655
authors.initials: CJ
authors.lastname: VandenBussche
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Olson
authors.affiliation: AC Camargo Cancer Centre, Sao Paulo, Brazil.
authors.forename: Isabela
authors.initials: I
authors.lastname: Cunha
authors.affiliation: Department of Urology, Osaka University, Osaka, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Fujita
authors.affiliation: Department of Pathology, Hacettepe University, Ankara, Turkey.
authors.forename: Dilek
authors.initials: D
authors.lastname: Ertoy
authors.affiliation: Departments of Urology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Trinity J
authors.initials: TJ
authors.lastname: Bivalacqua
authors.affiliation: Department of Oncology, Johns Hopkins University, Baltimore, MD, USA.|The Ludwig Center for Cancer Genetics and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kinzler
authors.affiliation: Department of Oncology, Johns Hopkins University, Baltimore, MD, USA.|The Ludwig Center for Cancer Genetics and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.|Departments of Urology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
authors.affiliation: Department of Oncology, Johns Hopkins University, Baltimore, MD, USA.|The Ludwig Center for Cancer Genetics and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
authors.forename: Nickolas
authors.initials: N
authors.lastname: Papadopoulos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D012189:Retrospective Studies; D019098:Telomerase / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D019098:Telomerase