The role of SPINK1 in ETS rearrangement-negative prostate cancers

Summary, in English

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.

• Author: 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; Hans Lilja; Victor E. Reuter; Phillip W. Kantoff; Peter T. Scardino; Mark A. Rubin; Anders Bjartell; Arul M. Chinnaiyan
• Department/s: Clinical Chemistry, Malmö; Urological cancer, Malmö
• Publishing year: 2008
• Language: English
• Pages: 519-528
• Publication/Series: Cancer Cell
• Volume: 13
• Issue: 6
• Links: http://dx.doi.org/10.1016/j.ccr.2008.04.016
• Document type: Journal article
• Publisher: Cell Press
• Topic: Cancer and Oncology
• Keywords: CELLBIO; HUMDISEASE
• Status: Published
• Research group: Clinical Chemistry, Malmö; Urological cancer, Malmö
• ISBN/ISSN/Other: ISSN: 1878-3686