title: Detection of TERT promoter mutations in primary adenocarcinoma of the urinary bladder.
abstract: TERT promoter mutations (TERT-mut) have been detected in 60% to 80% of urothelial carcinomas. A molecular urine-based screening assay for the detection of TERT-mut is currently being pursued by our group and others. A small but significant number of bladder carcinomas are adenocarcinoma. The current study assesses the incidence of TERT-mut in primary adenocarcinomas of urinary bladder. A retrospective search of our institutional pathology records identified 23 cystectomy specimens with a diagnosis of adenocarcinoma (2000-2014). All slides were reviewed by a senior urologic pathologist to confirm tumor type and select a representative formalin-fixed, paraffin-embedded block for mutational analysis. Adequate material for DNA testing was available in 14 cases (7 enteric type and 7 not otherwise specified). TERT-mut sequencing analysis was performed using previously described SafeSeq technique. Overall, 28.5% of primary adenocarcinoma harbored TERT-mut. Interestingly, 57% of nonenteric adenocarcinomas were mutation positive, whereas none of the enteric-type tumors harbored mutations. Similar to urothelial carcinoma, we found a relatively higher rate of TERT-mut among nonenteric-type adenocarcinomas further supporting the potential utility of TERT-mut urine-based screening assay for bladder cancer.
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD 21287.
authors.forename: Morgan L
authors.initials: ML
authors.lastname: Cowan
authors.affiliation: Department of Oncology, Johns Hopkins University, Baltimore, MD 21287; Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231.
authors.forename: Simeon
authors.initials: S
authors.lastname: Springer
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD 21287.
authors.forename: Doreen
authors.initials: D
authors.lastname: Nguyen
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD 21287.
authors.forename: Diana
authors.initials: D
authors.lastname: Taheri
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD 21287.
authors.forename: Gunes
authors.initials: G
authors.lastname: Guner
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD 21287.
authors.forename: Maria Angelica
authors.initials: MA
authors.lastname: Mendoza Rodriguez
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231.
authors.forename: Isaac
authors.initials: I
authors.lastname: Kinde
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD 21287.
authors.forename: Maria
authors.initials: M
authors.lastname: Del Carmen Rodriguez Pena
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD 21287.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: VandenBussche
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD 21287.
authors.forename: Mathew T
authors.initials: MT
authors.lastname: Olson
authors.affiliation: AC Camargo Cancer Centre, Sao Paulo, Brazil, 01509-010.
authors.forename: Isabela
authors.initials: I
authors.lastname: Cunha
authors.affiliation: Department of Urology, Osaka University, Osaka, Japan 565-0871.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Fujita
authors.affiliation: Department of Pathology, Hacettepe University, Ankara, Turkey 06100.
authors.forename: Dilek
authors.initials: D
authors.lastname: Ertoy
authors.affiliation: Department of Oncology, Johns Hopkins University, Baltimore, MD 21287; Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kinzler
authors.affiliation: Department of Urology, Johns Hopkins University, Baltimore, MD 21287.
authors.forename: Trinity
authors.initials: T
authors.lastname: Bivalacqua
authors.affiliation: Department of Oncology, Johns Hopkins University, Baltimore, MD 21287; Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231.
authors.forename: Nickolas
authors.initials: N
authors.lastname: Papadopoulos
authors.affiliation: Department of Oncology, Johns Hopkins University, Baltimore, MD 21287; Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231.
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD 21287; Department of Urology, Johns Hopkins University, Baltimore, MD 21287. Electronic address: gnetto1@jhmi.edu.
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D015142:Baltimore; D014408:Biomarkers, Tumor / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D019098:Telomerase / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C509186:TERT protein, human; D019098:Telomerase
keywords: Adenocarcinoma; Bladder carcinoma; Mutation; TERT; Telomerase; Telomerase reverse transcriptase