Loss of Wave1 gene defines a subtype of lethal prostate cancer

Oncotarget. 2015 May 20;6(14):12383-91. doi: 10.18632/oncotarget.3564.


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.

Keywords: WAVE; androgen receptor; castration resistance; genomics; prostate cancer.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Computational Biology
  • Drug Resistance, Neoplasm / genetics*
  • Humans
  • Male
  • Neoplasm Recurrence, Local / genetics
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Wiskott-Aldrich Syndrome Protein Family / genetics*


  • WASF1 protein, human
  • Wiskott-Aldrich Syndrome Protein Family