The Role of SPINK1 in ETS Rearrangement-Negative Prostate Cancers

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 Andrén, Katja Fall, Laura Johnson, John T. Wei, Rajal B. Shah, Hikmat Al-Ahmadie, James A. Eastham, Scott E. EggenerSamson W. Fine, Kristina Hotakainen, Ulf Håkan Stenman, Alex Tsodikov, William L. Gerald, Hans Lilja, Victor E. Reuter, Phillip W. Kantoff, Peter T. Scardino, Mark A. Rubin, Anders S. Bjartell, Arul M. Chinnaiyan

Research output: Contribution to journalArticle

230 Scopus citations

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 (∼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.

Original languageEnglish (US)
Pages (from-to)519-528
Number of pages10
JournalCancer Cell
Volume13
Issue number6
DOIs
StatePublished - Jun 10 2008
Externally publishedYes

Keywords

  • CELLBIO
  • HUMDISEASE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Tomlins, S. A., Rhodes, D. R., Yu, J., Varambally, S., Mehra, R., Perner, S., Demichelis, F., Helgeson, B. E., Laxman, B., Morris, D. S., Cao, Q., Cao, X., Andrén, O., Fall, K., Johnson, L., Wei, J. T., Shah, R. B., Al-Ahmadie, H., Eastham, J. A., ... Chinnaiyan, A. M. (2008). The Role of SPINK1 in ETS Rearrangement-Negative Prostate Cancers. Cancer Cell, 13(6), 519-528. https://doi.org/10.1016/j.ccr.2008.04.016