PMID- 25809148
OWN - NLM
STAT- MEDLINE
DCOM- 20150717
LR  - 20220330
IS  - 1097-0045 (Electronic)
IS  - 0270-4137 (Print)
IS  - 0270-4137 (Linking)
VI  - 75
IP  - 10
DP  - 2015 Jul 1
TI  - Molecular profiling of ETS and non-ETS aberrations in prostate cancer patients 
      from northern India.
PG  - 1051-62
LID - 10.1002/pros.22989 [doi]
AB  - 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  approximately 1% and  approximately 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.
CI  - (c) 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.
FAU - Ateeq, Bushra
AU  - Ateeq B
AD  - Department of Biological Sciences and Bioengineering, Indian Institute of 
      Technology, Kanpur, India.
FAU - Kunju, Lakshmi P
AU  - Kunju LP
AD  - Michigan Center for Translational Pathology, University of Michigan Medical 
      School, Ann Arbor, Michigan.
AD  - Department of Pathology, University of Michigan, University of Michigan Medical 
      School, Ann Arbor, Michigan.
AD  - Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, 
      Michigan.
FAU - Carskadon, Shannon L
AU  - Carskadon SL
AD  - Michigan Center for Translational Pathology, University of Michigan Medical 
      School, Ann Arbor, Michigan.
AD  - Department of Pathology, University of Michigan, University of Michigan Medical 
      School, Ann Arbor, Michigan.
FAU - Pandey, Swaroop K
AU  - Pandey SK
AD  - Department of Biological Sciences and Bioengineering, Indian Institute of 
      Technology, Kanpur, India.
FAU - Singh, Geetika
AU  - Singh G
AD  - Department of Pathology, All India Institute of Medical Sciences, New Delhi, 
      India.
FAU - Pradeep, Immanuel
AU  - Pradeep I
AD  - Department of Pathology, All India Institute of Medical Sciences, New Delhi, 
      India.
FAU - Tandon, Vini
AU  - Tandon V
AD  - Digdarshika Pathology Laboratory, Lucknow, India.
FAU - Singhai, Atin
AU  - Singhai A
AD  - Department of Pathology, King George's Medical University, Lucknow, India.
FAU - Goel, Apul
AU  - Goel A
AD  - Department of Urology, King George's Medical University, Lucknow, India.
FAU - Amit, Sonal
AU  - Amit S
AD  - Department of Pathology, GSVM Medical College, Kanpur, India.
FAU - Agarwal, Asha
AU  - Agarwal A
AD  - Department of Pathology, GSVM Medical College, Kanpur, India.
FAU - Dinda, Amit K
AU  - Dinda AK
AD  - Department of Pathology, All India Institute of Medical Sciences, New Delhi, 
      India.
FAU - Seth, Amlesh
AU  - Seth A
AD  - Department of Urology, All India Institute of Medical Sciences, New Delhi, India.
FAU - Tsodikov, Alexander
AU  - Tsodikov A
AD  - Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
FAU - Chinnaiyan, Arul M
AU  - Chinnaiyan AM
AD  - Michigan Center for Translational Pathology, University of Michigan Medical 
      School, Ann Arbor, Michigan.
AD  - Department of Pathology, University of Michigan, University of Michigan Medical 
      School, Ann Arbor, Michigan.
AD  - Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, 
      Michigan.
AD  - Howard Hughes Medical Institute, University of Michigan Medical School, Ann 
      Arbor, Michigan.
FAU - Palanisamy, Nallasivam
AU  - Palanisamy N
AD  - Michigan Center for Translational Pathology, University of Michigan Medical 
      School, Ann Arbor, Michigan.
AD  - Department of Urology, Henry Ford Health System, Detroit, Michigan.
LA  - eng
GR  - Wellcome Trust/United Kingdom
GR  - IA/S(I)/12/2/500635/WTDBT_/DBT-Wellcome Trust India Alliance/India
GR  - P50 CA186786/CA/NCI NIH HHS/United States
GR  - IA/I(S)/12/2/500635/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20150323
PL  - United States
TA  - Prostate
JT  - The Prostate
JID - 8101368
RN  - 0 (Carrier Proteins)
RN  - 0 (ERG protein, human)
RN  - 0 (Proto-Oncogene Proteins c-ets)
RN  - 0 (SPINK1 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcriptional Regulator ERG)
RN  - 50936-63-5 (Trypsin Inhibitor, Kazal Pancreatic)
RN  - EC 2.7.11.1 (raf Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
EIN - Prostate. 2021 May;81(6):357-358. PMID: 33683724
MH  - Carrier Proteins/genetics
MH  - Gene Deletion
MH  - Gene Expression
MH  - Gene Expression Profiling
MH  - Gene Rearrangement/genetics
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - In Situ Hybridization, Fluorescence
MH  - India
MH  - Male
MH  - PTEN Phosphohydrolase
MH  - Prognosis
MH  - Prostatic Neoplasms/*genetics
MH  - Proto-Oncogene Proteins c-ets/*genetics
MH  - Trans-Activators/genetics
MH  - Transcriptional Regulator ERG
MH  - Trypsin Inhibitor, Kazal Pancreatic
MH  - raf Kinases/genetics
PMC - PMC4832366
OTO - NOTNLM
OT  - PTEN
OT  - RAF kinase
OT  - SPINK1
OT  - TMPRSS2-ERG
OT  - genetic rearrangements
EDAT- 2015/03/27 06:00
MHDA- 2015/07/18 06:00
PMCR- 2016/04/15
CRDT- 2015/03/27 06:00
PHST- 2014/11/24 00:00 [received]
PHST- 2015/02/02 00:00 [accepted]
PHST- 2015/03/27 06:00 [entrez]
PHST- 2015/03/27 06:00 [pubmed]
PHST- 2015/07/18 06:00 [medline]
PHST- 2016/04/15 00:00 [pmc-release]
AID - PROS22989 [pii]
AID - 10.1002/pros.22989 [doi]
PST - ppublish
SO  - Prostate. 2015 Jul 1;75(10):1051-62. doi: 10.1002/pros.22989. Epub 2015 Mar 23.