title: Loss of Wave1 gene defines a subtype of lethal prostate cancer.
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.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.|Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Adam G
authors.initials: AG
authors.lastname: Sowalsky
authors.affiliation: Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sager
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Schaefer
authors.affiliation: Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Gennady
authors.initials: G
authors.lastname: Bratslavsky
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.|Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.|Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Pandolfi
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.|Cancer Research Institute, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Balk
authors.affiliation: Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.|Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Leszek
authors.initials: L
authors.lastname: Kotula
mesh_terms: D019295:Computational Biology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics* / Q000473:pathology; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000235:genetics*
chemical_list: C114864:WASF1 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family
keywords: WAVE; androgen receptor; castration resistance; genomics; prostate cancer