Literature DB >> 18538735

The role of SPINK1 in ETS rearrangement-negative prostate cancers.

Scott A Tomlins1, 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 Eggener, Samson 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.   

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 ( approximately 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.

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Year:  2008        PMID: 18538735      PMCID: PMC2732022          DOI: 10.1016/j.ccr.2008.04.016

Source DB:  PubMed          Journal:  Cancer Cell        ISSN: 1535-6108            Impact factor:   31.743


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