The role of SPINK1 in ETS rearrangement-negative prostate cancers

被引：254

作者：

Tomlins, Scott A. ^{[1
,3
]}

Rhodes, Daniel R. ^{[1
,3
,4
]}

Yu, Jianjun ^{[1
,4
]}

Varambally, Sooryanarayana ^{[1
,3
,6
]}

Mehra, Rohit ^{[1
,3
,6
]}

Perner, Sven ^{[7
,11
]}

Demichelis, Francesca ^{[8
,9
]}

Helgeson, Beth E. ^{[1
,3
]}

Laxman, Bharathi ^{[1
,3
]}

Morris, David S.

Cao, Qi ^{[1
,3
]}

Cao, Xuhong ^{[1
,2
]}

Andren, Ove ^{[12
]}

Fall, Katja ^{[13
]}

Johnson, Laura ^{[9
]}

Wei, John T. ^{[5
]}

Shah, Raja B. ^{[1
,3
,5
,6
]}

Al-Ahmadie, Hikmat ^{[14
]}

Eastham, James A. ^{[15
]}

Eggener, Scott E. ^{[15
]}

Fine, Samson W. ^{[14
]}

Hotakainen, Kristina ^{[17
]}

Stenman, Ulf-Hakan ^{[17
]}

Tsodikov, Alex ^{[1
,4
,6
,18
]}

Gerald, William L. ^{[14
]}

Lilja, Hans ^{[15
,16
,19
]}

Reuter, Victor E. ^{[14
]}

Kantoff, Phillip W. ^{[7
,9
,10
]}

Scardino, Peter T. ^{[15
]}

Rubin, Mark A. ^{[8
,9
,10
]}

Bjartell, Anders S. ^{[15
,20
]}

Chinnaiyan, Arul M. ^{[1
,2
,3
,4
,5
,6
]}

机构：

[1] Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Sch Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Sch Med, Ctr Computat Med & Biol, Ann Arbor, MI 48109 USA

[5] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA

[6] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA

[7] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[8] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[9] Harvard Univ, Sch Med, Boston, MA 02115 USA

[10] Dana Farber Canc Inst, Boston, MA 02115 USA

[11] Univ Hosp Ulm, Inst Pathol, D-89081 Ulm, Germany

[12] Orebro Univ Hosp, Dept Urol, SE-70185 Orebro, Sweden

[13] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden

[14] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA

[15] Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10065 USA

[16] Mem Sloan Kettering Canc Ctr, Dept Surg, Dept Clin Labs & Med, New York, NY 10065 USA

[17] Univ Helsinki, Cent Hosp, Dept Clin Chem, FIN-00290 Helsinki, Finland

[18] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA

[19] Lund Univ, Univ Hosp UMAS, Dept Lab Med, SE-20502 Malmo, Sweden

[20] Lund Univ, Univ Hosp UMAS, Dept Urol, SE-20502 Malmo, Sweden

来源：

CANCER CELL | 2008年 / 13卷 / 06期

关键词：

D O I：

10.1016/j.ccr.2008.04.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：519 / 528

页数：10

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