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The role of SPINK1 in ETS rearrangement-negative prostate cancers

Tomlins, Scott A.; Rhodes, Daniel R.; Yu, Jianjun; Varambally, Sooryanarayana; Mehra, Rohit; Perner, Sven; Demichelis, Francesca; Helgeson, Beth E.; Laxman, Bharathi and Morris, David S., et al. (2008) In Cancer Cell 13(6). p.519-528
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... (More)
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. (Less)
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@article{a873ab94-04a3-43b5-bf1a-499d40d43a90,
  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.},
  author       = {Tomlins, Scott A. and Rhodes, Daniel R. and Yu, Jianjun and Varambally, Sooryanarayana and Mehra, Rohit and Perner, Sven and Demichelis, Francesca and Helgeson, Beth E. and Laxman, Bharathi and Morris, David S. and Cao, Qi and Cao, Xuhong and Andren, Ove and Fall, Katja and Johnson, Laura and Wei, John T. and Shah, Raja B. and Al-Ahmadie, Hikmat and Eastham, James A. and Eggener, Scott E. and Fine, Samson W. and Hotakainen, Kristina and Stenman, Ulf-Hakan and Tsodikov, Alex and Gerald, William L. and Lilja, Hans and Reuter, Victor E. and Kantoff, Phillip W. and Scardino, Peter T. and Rubin, Mark A. and Bjartell, Anders and Chinnaiyan, Arul M.},
  issn         = {1878-3686},
  keyword      = {CELLBIO,HUMDISEASE},
  language     = {eng},
  number       = {6},
  pages        = {519--528},
  publisher    = {Cell Press},
  series       = {Cancer Cell},
  title        = {The role of SPINK1 in ETS rearrangement-negative prostate cancers},
  url          = {http://dx.doi.org/10.1016/j.ccr.2008.04.016},
  volume       = {13},
  year         = {2008},
}