Molecular profiling of clear cell adenocarcinoma of the urinary tract

Chieh Yu Lin, Atif Saleem, Henning Stehr, James L. Zehnder, Benjamin A. Pinsky, Christian A. Kunder

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Clear cell adenocarcinoma (CCA) of the urinary tract is a rare type of malignancy whose molecular profiles remain undefined. Here we reported an integrated clinicopathologic and molecular profiling analysis of four cases of clear cell adenocarcinoma arising in the urethra or the bladder. Utilizing a clinically validated 130-gene exon-sequencing assay, we identified recurrent pathogenic PIK3CA (p. E545K) and KRAS (p.G12D) variants in three of four (75%) of the cases. In addition, an APC variant (P.S2310X), a TP53 variant (p.R273C), and a MYC amplification event were identified. The only CCA case without either PIK3CA or KRAS variants has a distinct pathogenesis through BK virus, demonstrated by positive BK virus PCR and SV40 immunohistochemistry. The novel finding of recurrent variants in the PI3K/AKT/mTOR pathway provides not only insights into oncogenesis but also potential clinical therapeutic targets for patients with clear cell adenocarcinoma of the urinary tract.

Original languageEnglish
Pages (from-to)727-734
Number of pages8
JournalVirchows Archiv
Volume475
Issue number6
DOIs
StatePublished - Dec 1 2019

Keywords

  • Clear cell adenocarcinoma
  • KRAS
  • Molecular profiling
  • PIK3CA
  • Urinary tract

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