title: Molecular profiling of ETS and non-ETS aberrations in prostate cancer patients from northern India.
abstract: BACKGROUND
  Molecular stratification of prostate cancer (PCa) based on genetic aberrations including ETS or RAF gene-rearrangements, PTEN deletion, and SPINK1 over-expression show clear prognostic and diagnostic utility. Gene rearrangements involving ETS transcription factors are frequent pathogenetic somatic events observed in PCa. Incidence of ETS rearrangements in Caucasian PCa patients has been reported, however, occurrence in Indian population is largely unknown. The aim of this study was to determine the prevalence of the ETS and RAF kinase gene rearrangements, SPINK1 over-expression, and PTEN deletion in this cohort.
  
  
  METHODS
  In this multi-center study, formalin-fixed paraffin embedded (FFPE) PCa specimens (n = 121) were procured from four major medical institutions in India. The tissues were sectioned and molecular profiling was done using immunohistochemistry (IHC), RNA in situ hybridization (RNA-ISH) and/or fluorescence in situ hybridization (FISH).
  
  
  RESULTS
  ERG over-expression was detected in 48.9% (46/94) PCa specimens by IHC, which was confirmed in a subset of cases by FISH. Among other ETS family members, while ETV1 transcript was detected in one case by RNA-ISH, no alteration in ETV4 was observed. SPINK1 over-expression was observed in 12.5% (12/96) and PTEN deletion in 21.52% (17/79) of the total PCa cases. Interestingly, PTEN deletion was found in 30% of the ERG-positive cases (P = 0.017) but in only one case with SPINK1 over-expression (P = 0.67). BRAF and RAF1 gene rearrangements were detected in ∼1% and ∼4.5% of the PCa cases, respectively.
  
  
  CONCLUSIONS
  This is the first report on comprehensive molecular profiling of the major spectrum of the causal aberrations in Indian men with PCa. Our findings suggest that ETS gene rearrangement and SPINK1 over-expression patterns in North Indian population largely resembled those observed in Caucasian population but differed from Japanese and Chinese PCa patients. The molecular profiling data presented in this study could help in clinical decision-making for the pursuit of surgery, diagnosis, and in selection of therapeutic intervention.
authors: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, India.
authors: Bushra
authors: B
authors: Ateeq
authors: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan.|Department of Pathology, University of Michigan, University of Michigan Medical School, Ann Arbor, Michigan.|Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan.
authors: Lakshmi P
authors: LP
authors: Kunju
authors: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan.|Department of Pathology, University of Michigan, University of Michigan Medical School, Ann Arbor, Michigan.
authors: Shannon L
authors: SL
authors: Carskadon
authors: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, India.
authors: Swaroop K
authors: SK
authors: Pandey
authors: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors: Geetika
authors: G
authors: Singh
authors: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors: Immanuel
authors: I
authors: Pradeep
authors: Digdarshika Pathology Laboratory, Lucknow, India.
authors: Vini
authors: V
authors: Tandon
authors: Department of Pathology, King George's Medical University, Lucknow, India.
authors: Atin
authors: A
authors: Singhai
authors: Department of Urology, King George's Medical University, Lucknow, India.
authors: Apul
authors: A
authors: Goel
authors: Department of Pathology, GSVM Medical College, Kanpur, India.
authors: Sonal
authors: S
authors: Amit
authors: Department of Pathology, GSVM Medical College, Kanpur, India.
authors: Asha
authors: A
authors: Agarwal
authors: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors: Amit K
authors: AK
authors: Dinda
authors: Department of Urology, All India Institute of Medical Sciences, New Delhi, India.
authors: Amlesh
authors: A
authors: Seth
authors: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
authors: Alexander
authors: A
authors: Tsodikov
authors: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan.|Department of Pathology, University of Michigan, University of Michigan Medical School, Ann Arbor, Michigan.|Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan.|Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, Michigan.
authors: Arul M
authors: AM
authors: Chinnaiyan
authors: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan.|Department of Urology, Henry Ford Health System, Detroit, Michigan.
authors: Nallasivam
authors: N
authors: Palanisamy
mesh_terms: D002352:Carrier Proteins / Q000235:genetics; D017353:Gene Deletion; D015870:Gene Expression; D020869:Gene Expression Profiling; D015321:Gene Rearrangement / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D007194:India; D008297:Male; D051059:PTEN Phosphohydrolase; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics; D000071230:Transcriptional Regulator ERG; D014359:Trypsin Inhibitor, Kazal Pancreatic; D048490:raf Kinases / Q000235:genetics
chemical_list: D002352:Carrier Proteins; C072312:ERG protein, human; D050783:Proto-Oncogene Proteins c-ets; C486642:SPINK1 protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014359:Trypsin Inhibitor, Kazal Pancreatic; D048490:raf Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: PTEN; RAF kinase; SPINK1; TMPRSS2-ERG; genetic rearrangements