title: Determining the frequency of pathogenic germline variants from exome sequencing in patients with castrate-resistant prostate cancer.
abstract: OBJECTIVE
  To determine the frequency of pathogenic inherited mutations in 157 select genes from patients with metastatic castrate-resistant prostate cancer (mCRPC).
  
  
  METHODS
  Observational.
  
  
  METHODS
  Multisite US-based cohort.
  
  
  METHODS
  Seventy-one adult male patients with histological confirmation of prostate cancer, and had progressive disease while on androgen deprivation therapy.
  
  
  RESULTS
  Twelve patients (17.4%) showed evidence of carrying pathogenic or likely pathogenic germline variants in the ATM, ATR, BRCA2, FANCL, MSR1, MUTYH, RB1, TSHR and WRN genes. All but one patient opted in to receive clinically actionable results at the time of study initiation. We also found that pathogenic germline BRCA2 variants appear to be enriched in mCRPC compared to familial prostate cancers.
  
  
  CONCLUSIONS
  Pathogenic variants in cancer-susceptibility genes are frequently observed in patients with mCRPC. A substantial proportion of patients with mCRPC or their family members would derive clinical utility from mutation screening.
  
  
  BACKGROUND
  NCT01953640; Results.
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Steven N
authors.initials: SN
authors.lastname: Hart
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Marissa S
authors.initials: MS
authors.lastname: Ellingson
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Schahl
authors.affiliation: Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Vedell
authors.affiliation: Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Carlson
authors.affiliation: Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Sinnwell
authors.affiliation: Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Poulami
authors.initials: P
authors.lastname: Barman
authors.affiliation: Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Hugues
authors.initials: H
authors.lastname: Sicotte
authors.affiliation: Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Jeanette E
authors.initials: JE
authors.lastname: Eckel-Passow
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Liguo
authors.initials: L
authors.lastname: Wang
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Krishna R
authors.initials: KR
authors.lastname: Kalari
authors.affiliation: Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Qin
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Kruisselbrink
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Rafael E
authors.initials: RE
authors.lastname: Jimenez
authors.affiliation: Division of Hematology/Oncology, Mayo Clinic, Mayo Clinic Cancer Center, Scottsdale, Arizona, USA.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Bryce
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Jacksonville, Florida, USA.
authors.forename: Winston
authors.initials: W
authors.lastname: Tan
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Weinshilboum
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Liewei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, USA.
authors.forename: Manish
authors.initials: M
authors.lastname: Kohli
mesh_terms: D000328:Adult; D000368:Aged; D024682:BRCA2 Protein / Q000235:genetics; D059472:Exome; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics* / Q000473:pathology
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D009363:Neoplasm Proteins
keywords: BRCA2; Cancer Risk; Genetic testing; Germline; Prostate cancer