title: Retrospective study testing next generation sequencing of selected cancer-associated genes in resected prostate cancer.
abstract: OBJECTIVE
  Prostate cancer (PCa) has a highly heterogeneous outcome. Beyond Gleason Score, Prostate Serum Antigen and tumor stage, nowadays there are no biological prognostic factors to discriminate between indolent and aggressive tumors.The most common known genomic alterations are the TMPRSS-ETS translocation and mutations in the PI3K, MAPK pathways and in p53, RB and c-MYC genes.The aim of this retrospective study was to identify by next generation sequencing the most frequent genetic variations (GVs) in localized and locally advanced PCa underwent prostatectomy and to investigate their correlation with clinical-pathological variables and disease progression.
  
  
  RESULTS
  Identified non-synonymous GVs included TP53 p.P72R (78% of tumors), two CSFR1 SNPs, rs2066934 and rs2066933 (70%), KDR p.Q472H (67%), KIT p.M541L (28%), PIK3CA p.I391M (19%), MET p.V378I (10%) and FGFR3 p.F384L/p.F386L (8%). TP53 p.P72R, MET p.V378I and CSFR1 SNPs were significantly associated with the HI risk group, TP53 and MET variations with T≥T2c. FGFR3 p.F384L/p.F386L was correlated with T≤T2b. MET p.V378I mutation, detected in 20% of HI risk patients, was associated with early biochemical recurrence.
  
  
  METHODS
  Nucleic acids were obtained from tissue samples of 30 high (HI) and 30 low-intermediate (LM) risk patients, according to D'Amico criteria. Genomic DNA was explored with the Ion_AmpliSeq_Cancer_Hotspot_Panel_v.2 including 50 cancer-associated genes. GVs with allelic frequency (AF) ≥10%, affecting protein function or previously associated with cancer, were correlated with clinical-pathological variables.
  
  
  CONCLUSIONS
  Our results confirm a complex mutational profile in PCa, supporting the involvement of TP53, MET, FGFR3, CSF1R GVs in tumor progression and aggressiveness.
authors.affiliation: University of Turin, Department of Oncology, Orbassano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Lo Iacono
authors.affiliation: University of Turin, Department of Oncology, Orbassano, Italy.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Buttigliero
authors.affiliation: University of Turin, Department of Oncology, Orbassano, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Monica
authors.affiliation: University of Turin, Department of Oncology, Orbassano, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Bollito
authors.affiliation: University of Turin, Department of Oncology, Orbassano, Italy.
authors.forename: Diletta
authors.initials: D
authors.lastname: Garrou
authors.affiliation: University of Turin, Department of Oncology, Orbassano, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Cappia
authors.affiliation: University of Turin, Department of Oncology, Orbassano, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Rapa
authors.affiliation: University of Turin, Department of Oncology, Orbassano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Vignani
authors.affiliation: University of Turin, Department of Oncology, Orbassano, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bertaglia
authors.affiliation: University of Turin, Department of Oncology, Orbassano, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Fiori
authors.affiliation: University of Turin, Department of Oncology, Orbassano, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
authors.affiliation: University of Turin, Department of Oncology, Orbassano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.affiliation: University of Turin, Department of Oncology, Orbassano, Italy.
authors.forename: Giorgio V
authors.initials: GV
authors.lastname: Scagliotti
authors.affiliation: University of Turin, Department of Oncology, Orbassano, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Porpiglia
authors.affiliation: University of Turin, Department of Oncology, Orbassano, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tucci
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D018450:Disease Progression; D005500:Follow-Up Studies; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor
keywords: genetic characterization; next generation sequencing; precision medicine; prognostic factors; prostate cancer