title: Primary urethral clear-cell adenocarcinoma: comprehensive analysis by surgical pathology, cytopathology, and next-generation sequencing.
abstract: Primary clear-cell adenocarcinoma of the urethra, a rare tumor that histomorphologically resembles clear-cell carcinoma of the female genital tract, occurs predominantly in women and is associated with a relatively poor prognosis. The histogenesis of this rare urethral neoplasm has not been completely resolved, but it is thought to arise from either müllerian rests or metaplastic urothelium. Herein, we present comprehensive surgical pathological and cytopathological findings from a patient with primary urethral clear-cell adenocarcinoma and describe next-generation sequencing results for this patient's unique tumor-the first such reported characterization of molecular aberrations in urethral clear-cell adenocarcinoma at the transcriptomic and genomic levels. Transcriptome analysis revealed novel gene fusion candidates, including ANKRD28-FNDC3B. Whole-exome analysis demonstrated focal copy number loss at the SMAD4 and ARID2 loci and 38 somatic mutations, including a truncating mutation in ATM and a novel nonsynonymous mutation in ALK.
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, Michigan; Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, Michigan; Michigan Center for Translational Pathology, Ann Arbor, Michigan. Electronic address: mrohit@med.umich.edu.
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, Michigan; Michigan Center for Translational Pathology, Ann Arbor, Michigan.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Vats
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, Michigan; Michigan Center for Translational Pathology, Ann Arbor, Michigan.
authors.forename: Shanker
authors.initials: S
authors.lastname: Kalyana-Sundaram
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Udager
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Michael
authors.initials: M
authors.lastname: Roh
authors.affiliation: Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, Michigan; Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Ajjai
authors.initials: A
authors.lastname: Alva
authors.affiliation: Michigan Center for Translational Pathology, Ann Arbor, Michigan; Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jincheng
authors.initials: J
authors.lastname: Pan
authors.affiliation: Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, Michigan; Michigan Center for Translational Pathology, Ann Arbor, Michigan.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lonigro
authors.affiliation: Michigan Center for Translational Pathology, Ann Arbor, Michigan.
authors.forename: Javed
authors.initials: J
authors.lastname: Siddiqui
authors.affiliation: Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, Michigan; Department of Urology, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Alon
authors.initials: A
authors.lastname: Weizer
authors.affiliation: Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, Michigan; Department of Urology, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Lee
authors.affiliation: Michigan Center for Translational Pathology, Ann Arbor, Michigan.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Cao
authors.affiliation: Michigan Center for Translational Pathology, Ann Arbor, Michigan.
authors.forename: Yi-Mi
authors.initials: YM
authors.lastname: Wu
authors.affiliation: Michigan Center for Translational Pathology, Ann Arbor, Michigan.
authors.forename: Dan R
authors.initials: DR
authors.lastname: Robinson
authors.affiliation: Michigan Center for Translational Pathology, Ann Arbor, Michigan.
authors.forename: Saravana M
authors.initials: SM
authors.lastname: Dhanasekaran
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, Michigan; Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, Michigan; Michigan Center for Translational Pathology, Ann Arbor, Michigan; Department of Urology, University of Michigan Health System, Ann Arbor, Michigan; Howard Hughes Medical Institute, Ann Arbor, Michigan.
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D014408:Biomarkers, Tumor / Q000235:genetics*; D056915:DNA Copy Number Variations; D059472:Exome / Q000235:genetics; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010340:Pathology, Surgical; D017422:Sequence Analysis, DNA; D014523:Urethral Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor