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 language | English |
|---|---|
| Journal | Cancer Cell |
| Volume | 13 |
| Issue number | 6 |
| Pages (from-to) | 519-528 |
| Number of pages | 10 |
| ISSN | 1535-6108 |
| DOIs | |
| Publication status | Published - 10.06.2008 |
Funding
The authors thank Lei Wang, Anjana Menon, Xiaojun Jing, and Elise Nilsson for excellent technical support and Jill Macoska for the 22RV1 cell line. This work was supported in part by the US Department of Defense (grant W81XWH-08-1-0031 to A.M.C.); the National Institutes of Health (grant U54 DA021519-01A1 to A.M.C. and Prostate SPORE grant P50CA69568 to A.M.C. and R.B.S.); the Early Detection Research Network (grant UO1 CA111275-01 and grant UO1 CA113913 to A.M.C. and J.T.W.); the Prostate Cancer Foundation (S.A.T.); P50-CA92629 SPORE grant from the National Cancer Institute (P.W.K. and M.A.R.); Translational Cancer Research Fellowship Award TCR/05/009/2005 from the International Union Against Cancer (UICC); European Union 6th Framework contract LSHC-CT-2004-503011 (P-Mark); the Swedish Cancer Society (Projects 4294 and 3555); the Research Fund and the Cancer Research Fund of Malmö University Hospital; the Faculty of Medicine, Lund University; the Maud and Birger Gustavsson Foundation; the Gunnar Nilsson Cancer Foundation; the Finnish Cancer Foundation; the Sigrid Juselius Foundation; the Finnish Academy of Sciences; Helsinki University Central Hospital; and the University of Helsinki. S.A.T. is supported by a GPC Biotech Young Investigator Award from the Prostate Cancer Foundation. A.M.C. is supported by a Clinical Translational Research Award from the Burroughs Wellcome Foundation. S.A.T. and D.R.R. are Fellows of the University of Michigan Medical Scientist Training Program.
