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The Role of SPINK1 in ETS Rearrangement-Negative Prostate Cancers

2008; Cell Press; Volume: 13; Issue: 6 Linguagem: Inglês

10.1016/j.ccr.2008.04.016

1878-3686

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 A. 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, Philip W. Kantoff, Peter T. Scardino, Mark A. Rubin, Anders Bjartell, Arul M. Chinnaiyan,

Ubiquitin and proteasome pathways

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.