Oncotarget

Research Papers:

Loss of Wave1 gene defines a subtype of lethal prostate cancer

Adam G. Sowalsky _, Rebecca Sager, Rachel J. Schaefer, Gennady Bratslavsky, Pier Paolo Pandolfi, Steven P. Balk, Leszek Kotula

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Oncotarget. 2015; 6:12383-12391. https://doi.org/10.18632/oncotarget.3564

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Abstract

Adam G. Sowalsky1,5, Rebecca Sager2, Rachel J. Schaefer1, Gennady Bratslavsky3, Pier Paolo Pandolfi1,4,5, Steven P. Balk1,5, Leszek Kotula2,3

1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA

2Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA

3Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA

4Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA

5Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, MA 02215, USA

Correspondence to:

Leszek Kotula, e-mail: kotulal@upstate.edu

Adam G. Sowalsky, e-mail: asowalsk@bidmc.harvard.edu

Keywords: WAVE, prostate cancer, genomics, androgen receptor, castration resistance

Received: January 09, 2015     Accepted: March 13, 2015     Published: March 31, 2015

ABSTRACT

Genetic alterations involving TMPRSS2-ERG alterations and deletion of key tumor suppressor genes are associated with development and progression of prostate cancer (PCa). However, less defined are early events that may contribute to the development of high-risk metastatic prostate cancer. Bioinformatic analysis of existing tumor genomic data from PCa patients revealed that WAVE complex gene alterations are associated with a greater likelihood of prostate cancer recurrence. Further analysis of primary vs. castration resistant prostate cancer indicate that disruption of WAVE complex gene expression, and particularly WAVE1 gene (WASF1) loss, is also associated with castration resistance, where WASF1 is frequently co-deleted with PTEN and resists androgen deprivation therapy (ADT). Hence, we propose that WASF1 status defines a subtype of ADT-resistant patients. Better understanding of the effects of WAVE pathway disruption will lead to development of better diagnostic and treatment modalities.


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