The Role of SPINK1 in ETS Rearrangement-Negative Prostate Cancers

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 Johnson, John T. Wei, Rajal B. Shah, Hikmat Al-Ahmadie, James A. Eastham, Scott E. EggenerSamson 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

Research output: Contribution to journalArticle

221 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)519-528
Number of pages10
JournalCancer Cell
Volume13
Issue number6
DOIs
StatePublished - Jun 10 2008
Externally publishedYes

Fingerprint

Prostatic Neoplasms
Gene Fusion
Meta-Analysis
Neoplasms
Urine
Recurrence
Cell Line

Keywords

  • CELLBIO
  • HUMDISEASE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Tomlins, S. A., Rhodes, D. R., Yu, J., Varambally, S., Mehra, R., Perner, S., ... Chinnaiyan, A. M. (2008). The Role of SPINK1 in ETS Rearrangement-Negative Prostate Cancers. Cancer Cell, 13(6), 519-528. https://doi.org/10.1016/j.ccr.2008.04.016

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; Morris, David S.; Cao, Qi; Cao, Xuhong; Andrén, Ove; Fall, Katja; Johnson, Laura; Wei, John T.; Shah, Rajal B.; Al-Ahmadie, Hikmat; Eastham, James A.; Eggener, Scott E.; Fine, Samson W.; Hotakainen, Kristina; Stenman, Ulf Håkan; Tsodikov, Alex; Gerald, William L.; Lilja, Hans; Reuter, Victor E.; Kantoff, Phillip W.; Scardino, Peter T.; Rubin, Mark A.; Bjartell, Anders S.; Chinnaiyan, Arul M.

In: Cancer Cell, Vol. 13, No. 6, 10.06.2008, p. 519-528.

Research output: Contribution to journalArticle

Tomlins, SA, Rhodes, DR, Yu, J, Varambally, S, Mehra, R, Perner, S, Demichelis, F, Helgeson, BE, Laxman, B, Morris, DS, Cao, Q, Cao, X, Andrén, O, Fall, K, Johnson, L, Wei, JT, Shah, RB, Al-Ahmadie, H, Eastham, JA, Eggener, SE, Fine, SW, Hotakainen, K, Stenman, UH, Tsodikov, A, Gerald, WL, Lilja, H, Reuter, VE, Kantoff, PW, Scardino, PT, Rubin, MA, Bjartell, AS & Chinnaiyan, AM 2008, 'The Role of SPINK1 in ETS Rearrangement-Negative Prostate Cancers', Cancer Cell, vol. 13, no. 6, pp. 519-528. https://doi.org/10.1016/j.ccr.2008.04.016
Tomlins SA, Rhodes DR, Yu J, Varambally S, Mehra R, Perner S et al. The Role of SPINK1 in ETS Rearrangement-Negative Prostate Cancers. Cancer Cell. 2008 Jun 10;13(6):519-528. https://doi.org/10.1016/j.ccr.2008.04.016
Tomlins, Scott A. ; Rhodes, Daniel R. ; Yu, Jianjun ; Varambally, Sooryanarayana ; Mehra, Rohit ; Perner, Sven ; Demichelis, Francesca ; Helgeson, Beth E. ; Laxman, Bharathi ; Morris, David S. ; Cao, Qi ; Cao, Xuhong ; Andrén, Ove ; Fall, Katja ; Johnson, Laura ; Wei, John T. ; Shah, Rajal B. ; Al-Ahmadie, Hikmat ; Eastham, James A. ; Eggener, Scott E. ; Fine, Samson W. ; Hotakainen, Kristina ; Stenman, Ulf Håkan ; Tsodikov, Alex ; Gerald, William L. ; Lilja, Hans ; Reuter, Victor E. ; Kantoff, Phillip W. ; Scardino, Peter T. ; Rubin, Mark A. ; Bjartell, Anders S. ; Chinnaiyan, Arul M. / The Role of SPINK1 in ETS Rearrangement-Negative Prostate Cancers. In: Cancer Cell. 2008 ; Vol. 13, No. 6. pp. 519-528.
@article{596272b1aea44b8c9ba02472d9b2d12f,
title = "The Role of SPINK1 in ETS Rearrangement-Negative Prostate Cancers",
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.",
keywords = "CELLBIO, HUMDISEASE",
author = "Tomlins, {Scott A.} and Rhodes, {Daniel R.} and Jianjun Yu and Sooryanarayana Varambally and Rohit Mehra and Sven Perner and Francesca Demichelis and Helgeson, {Beth E.} and Bharathi Laxman and Morris, {David S.} and Qi Cao and Xuhong Cao and Ove Andr{\'e}n and Katja Fall and Laura Johnson and Wei, {John T.} and Shah, {Rajal B.} and Hikmat Al-Ahmadie and Eastham, {James A.} and Eggener, {Scott E.} and Fine, {Samson W.} and Kristina Hotakainen and Stenman, {Ulf H{\aa}kan} and Alex Tsodikov and Gerald, {William L.} and Hans Lilja and Reuter, {Victor E.} and Kantoff, {Phillip W.} and Scardino, {Peter T.} and Rubin, {Mark A.} and Bjartell, {Anders S.} and Chinnaiyan, {Arul M.}",
year = "2008",
month = "6",
day = "10",
doi = "10.1016/j.ccr.2008.04.016",
language = "English (US)",
volume = "13",
pages = "519--528",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "6",

}

TY - JOUR

T1 - The Role of SPINK1 in ETS Rearrangement-Negative Prostate Cancers

AU - Tomlins, Scott A.

AU - Rhodes, Daniel R.

AU - Yu, Jianjun

AU - Varambally, Sooryanarayana

AU - Mehra, Rohit

AU - Perner, Sven

AU - Demichelis, Francesca

AU - Helgeson, Beth E.

AU - Laxman, Bharathi

AU - Morris, David S.

AU - Cao, Qi

AU - Cao, Xuhong

AU - Andrén, Ove

AU - Fall, Katja

AU - Johnson, Laura

AU - Wei, John T.

AU - Shah, Rajal B.

AU - Al-Ahmadie, Hikmat

AU - Eastham, James A.

AU - Eggener, Scott E.

AU - Fine, Samson W.

AU - Hotakainen, Kristina

AU - Stenman, Ulf Håkan

AU - Tsodikov, Alex

AU - Gerald, William L.

AU - Lilja, Hans

AU - Reuter, Victor E.

AU - Kantoff, Phillip W.

AU - Scardino, Peter T.

AU - Rubin, Mark A.

AU - Bjartell, Anders S.

AU - Chinnaiyan, Arul M.

PY - 2008/6/10

Y1 - 2008/6/10

N2 - 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.

AB - 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.

KW - CELLBIO

KW - HUMDISEASE

UR - http://www.scopus.com/inward/record.url?scp=44449139593&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=44449139593&partnerID=8YFLogxK

U2 - 10.1016/j.ccr.2008.04.016

DO - 10.1016/j.ccr.2008.04.016

M3 - Article

C2 - 18538735

AN - SCOPUS:44449139593

VL - 13

SP - 519

EP - 528

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 6

ER -