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Molecular profiling of ETS and non‐ETS aberrations in prostate cancer patients from northern India
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 pathogenet...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832366/ https://www.ncbi.nlm.nih.gov/pubmed/25809148 http://dx.doi.org/10.1002/pros.22989 |
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author | Ateeq, Bushra Kunju, Lakshmi P. Carskadon, Shannon L. Pandey, Swaroop K. Singh, Geetika Pradeep, Immanuel Tandon, Vini Singhai, Atin Goel, Apul Amit, Sonal Agarwal, Asha Dinda, Amit K. Seth, Amlesh Tsodikov, Alexander Chinnaiyan, Arul M. Palanisamy, Nallasivam |
author_facet | Ateeq, Bushra Kunju, Lakshmi P. Carskadon, Shannon L. Pandey, Swaroop K. Singh, Geetika Pradeep, Immanuel Tandon, Vini Singhai, Atin Goel, Apul Amit, Sonal Agarwal, Asha Dinda, Amit K. Seth, Amlesh Tsodikov, Alexander Chinnaiyan, Arul M. Palanisamy, Nallasivam |
author_sort | Ateeq, Bushra |
collection | PubMed |
description | 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. Prostate 75:1051–1062, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc. |
format | Online Article Text |
id | pubmed-4832366 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-48323662016-04-20 Molecular profiling of ETS and non‐ETS aberrations in prostate cancer patients from northern India Ateeq, Bushra Kunju, Lakshmi P. Carskadon, Shannon L. Pandey, Swaroop K. Singh, Geetika Pradeep, Immanuel Tandon, Vini Singhai, Atin Goel, Apul Amit, Sonal Agarwal, Asha Dinda, Amit K. Seth, Amlesh Tsodikov, Alexander Chinnaiyan, Arul M. Palanisamy, Nallasivam Prostate Original Articles 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. Prostate 75:1051–1062, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc. John Wiley and Sons Inc. 2015-03-23 2015-07 /pmc/articles/PMC4832366/ /pubmed/25809148 http://dx.doi.org/10.1002/pros.22989 Text en © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Ateeq, Bushra Kunju, Lakshmi P. Carskadon, Shannon L. Pandey, Swaroop K. Singh, Geetika Pradeep, Immanuel Tandon, Vini Singhai, Atin Goel, Apul Amit, Sonal Agarwal, Asha Dinda, Amit K. Seth, Amlesh Tsodikov, Alexander Chinnaiyan, Arul M. Palanisamy, Nallasivam Molecular profiling of ETS and non‐ETS aberrations in prostate cancer patients from northern India |
title | Molecular profiling of ETS and non‐ETS aberrations in prostate cancer patients from northern India |
title_full | Molecular profiling of ETS and non‐ETS aberrations in prostate cancer patients from northern India |
title_fullStr | Molecular profiling of ETS and non‐ETS aberrations in prostate cancer patients from northern India |
title_full_unstemmed | Molecular profiling of ETS and non‐ETS aberrations in prostate cancer patients from northern India |
title_short | Molecular profiling of ETS and non‐ETS aberrations in prostate cancer patients from northern India |
title_sort | molecular profiling of ets and non‐ets aberrations in prostate cancer patients from northern india |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832366/ https://www.ncbi.nlm.nih.gov/pubmed/25809148 http://dx.doi.org/10.1002/pros.22989 |
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