title: SPOP mutations in prostate cancer across demographically diverse patient cohorts.
abstract: BACKGROUND
  Recurrent mutations in the Speckle-Type POZ Protein (SPOP) gene occur in up to 15% of prostate cancers. However, the frequency and features of cancers with these mutations across different populations is unknown.
  
  
  OBJECTIVE
  To investigate SPOP mutations across diverse cohorts and validate a series of assays employing high-resolution melting (HRM) analysis and Sanger sequencing for mutational analysis of formalin-fixed paraffin-embedded material.
  
  
  METHODS
  720 prostate cancer samples from six international cohorts spanning Caucasian, African American, and Asian patients, including both prostate-specific antigen-screened and unscreened populations, were screened for their SPOP mutation status. Status of SPOP was correlated to molecular features (ERG rearrangement, PTEN deletion, and CHD1 deletion) as well as clinical and pathologic features.
  
  
  CONCLUSIONS
  Overall frequency of SPOP mutations was 8.1% (4.6% to 14.4%), SPOP mutation was inversely associated with ERG rearrangement (P<.01), and SPOP mutant (SPOPmut) cancers had higher rates of CHD1 deletions (P<.01). There were no significant differences in biochemical recurrence in SPOPmut cancers. Limitations of this study include missing mutational data due to sample quality and lack of power to identify a difference in clinical outcomes.
  
  
  CONCLUSIONS
  SPOP is mutated in 4.6% to 14.4% of patients with prostate cancer across different ethnic and demographic backgrounds. There was no significant association between SPOP mutations with ethnicity, clinical, or pathologic parameters. Mutual exclusivity of SPOP mutation with ERG rearrangement as well as a high association with CHD1 deletion reinforces SPOP mutation as defining a distinct molecular subclass of prostate cancer.
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute of Precision Medicine, Weill Medical College of Cornell University, New York, NY.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Blattner
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute of Precision Medicine, Weill Medical College of Cornell University, New York, NY ; Department of Urology, Weill Medical College of Cornell University, New York, NY.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lee
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute of Precision Medicine, Weill Medical College of Cornell University, New York, NY.
authors.forename: Catherine
authors.initials: C
authors.lastname: O'Reilly
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute of Precision Medicine, Weill Medical College of Cornell University, New York, NY.
authors.forename: Kyung
authors.initials: K
authors.lastname: Park
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute of Precision Medicine, Weill Medical College of Cornell University, New York, NY.
authors.forename: Theresa Y
authors.initials: TY
authors.lastname: MacDonald
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute of Precision Medicine, Weill Medical College of Cornell University, New York, NY.
authors.forename: Francesca
authors.initials: F
authors.lastname: Khani
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute of Precision Medicine, Weill Medical College of Cornell University, New York, NY.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Turner
authors.affiliation: Department of Biostatistics and Epidemiology, Weill Medical College of Cornell University and New York-Presbyterian Hospital, New York, NY.
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Chiu
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wild
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Igor
authors.initials: I
authors.lastname: Dolgalev
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Adriana
authors.initials: A
authors.lastname: Heguy
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute of Precision Medicine, Weill Medical College of Cornell University, New York, NY ; Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, NY ; Institute for Precision Medicine, Weill Medical College of Cornell University, New York, NY.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sboner
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute of Precision Medicine, Weill Medical College of Cornell University, New York, NY ; Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, NY.
authors.forename: Sinan
authors.initials: S
authors.lastname: Ramazangolu
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Haley
authors.initials: H
authors.lastname: Hieronymus
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Charles
authors.initials: C
authors.lastname: Sawyers
authors.affiliation: Department of Urology, Weill Medical College of Cornell University, New York, NY.
authors.forename: Ashutosh K
authors.initials: AK
authors.lastname: Tewari
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.affiliation: Department of Pathology, Kyungpook National University School of Medicine, Daegu, South Korea.
authors.forename: Ghil Suk
authors.initials: GS
authors.lastname: Yoon
authors.affiliation: Department of Pathology, School of Medicine, Catholic University of Daegu, Daegu, South Korea.
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Known
authors.affiliation: School of Health and Medical Sciences, Örebro University, Örebro, Sweden ; Department of Urology, Örebro University Hospital, Örebro, Sweden.
authors.forename: Ove
authors.initials: O
authors.lastname: Andrén
authors.affiliation: Departments of Clinical Epidemiology and Biostatistics, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
authors.forename: Katja
authors.initials: K
authors.lastname: Fall
authors.affiliation: Institute for Precision Medicine, Weill Medical College of Cornell University, New York, NY ; Centre for Integrative Biology, University of Trento, Trento, Italy.
authors.forename: Francecsa
authors.initials: F
authors.lastname: Demichelis
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute of Precision Medicine, Weill Medical College of Cornell University, New York, NY.
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Mosquera
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute of Precision Medicine, Weill Medical College of Cornell University, New York, NY ; Department of Urology, Weill Medical College of Cornell University, New York, NY.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Robinson
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute of Precision Medicine, Weill Medical College of Cornell University, New York, NY ; Department of Urology, Weill Medical College of Cornell University, New York, NY.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Barbieri
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute of Precision Medicine, Weill Medical College of Cornell University, New York, NY ; Department of Urology, Weill Medical College of Cornell University, New York, NY ; Institute for Precision Medicine, Weill Medical College of Cornell University, New York, NY.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004265:DNA Helicases / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
chemical_list: D004268:DNA-Binding Proteins; C072312:ERG protein, human; D009687:Nuclear Proteins; D012097:Repressor Proteins; C509761:SPOP protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D004265:DNA Helicases; C080359:CHD1 protein, human