The role of SPINK1 in ETS rearrangement-negative prostate cancers

Research output: Contribution to journalArticle

Abstract

ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers (similar to 10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers.

Details

Authors
  • Scott A. Tomlins
  • Daniel R. Rhodes
  • Jianjun Yu
  • Sooryanarayana Varambally
  • Rohit Mehra
  • Sven Perner
  • Francesca Demichelis
  • Beth E. Helgeson
  • Bharathi Laxman
  • David S. Morris
  • Qi Cao
  • Xuhong Cao
  • Ove Andren
  • Katja Fall
  • Laura Johnson
  • John T. Wei
  • Raja B. Shah
  • Hikmat Al-Ahmadie
  • James A. Eastham
  • Scott E. Eggener
  • Samson W. Fine
  • Kristina Hotakainen
  • Ulf-Hakan Stenman
  • Alex Tsodikov
  • William L. Gerald
  • Victor E. Reuter
  • Phillip W. Kantoff
  • Peter T. Scardino
  • Mark A. Rubin
  • Arul M. Chinnaiyan
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • CELLBIO, HUMDISEASE
Original languageEnglish
Pages (from-to)519-528
JournalCancer Cell
Volume13
Issue number6
Publication statusPublished - 2008
Publication categoryResearch
Peer-reviewedYes