Splice variants as novel targets in pancreatic ductal adenocarcinoma

Abstract Despite a wealth of genomic information, a comprehensive alternative splicing (AS) analysis of pancreatic ductal adenocarcinoma (PDAC) has not been performed yet. In the present study, we assessed whole exome-based transcriptome and AS profiles of 43 pancreas tissues using Affymetrix exon a...

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Autores principales:	Jun Wang, Laurent Dumartin, Andrea Mafficini, Pinar Ulug, Ajanthah Sangaralingam, Namaa Audi Alamiry, Tomasz P. Radon, Roberto Salvia, Rita T. Lawlor, Nicholas R. Lemoine, Aldo Scarpa, Claude Chelala, Tatjana Crnogorac-Jurcevic
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5e296d11dc7c438894ef3382cb3a4a71
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spelling	oai:doaj.org-article:5e296d11dc7c438894ef3382cb3a4a712021-12-02T15:05:14ZSplice variants as novel targets in pancreatic ductal adenocarcinoma10.1038/s41598-017-03354-z2045-2322https://doaj.org/article/5e296d11dc7c438894ef3382cb3a4a712017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03354-zhttps://doaj.org/toc/2045-2322Abstract Despite a wealth of genomic information, a comprehensive alternative splicing (AS) analysis of pancreatic ductal adenocarcinoma (PDAC) has not been performed yet. In the present study, we assessed whole exome-based transcriptome and AS profiles of 43 pancreas tissues using Affymetrix exon array. The AS analysis of PDAC indicated on average two AS probe-sets (ranging from 1–28) in 1,354 significantly identified protein-coding genes, with skipped exon and alternative first exon being the most frequently utilised. In addition to overrepresented extracellular matrix (ECM)-receptor interaction and focal adhesion that were also seen in transcriptome differential expression (DE) analysis, Fc gamma receptor-mediated phagocytosis and axon guidance AS genes were also highly represented. Of note, the highest numbers of AS probe-sets were found in collagen genes, which encode the characteristically abundant stroma seen in PDAC. We also describe a set of 37 ‘hypersensitive’ genes which were frequently targeted by somatic mutations, copy number alterations, DE and AS, indicating their propensity for multidimensional regulation. We provide the most comprehensive overview of the AS landscape in PDAC with underlying changes in the spliceosomal machinery. We also collate a set of AS and DE genes encoding cell surface proteins, which present promising diagnostic and therapeutic targets in PDAC.Jun WangLaurent DumartinAndrea MafficiniPinar UlugAjanthah SangaralingamNamaa Audi AlamiryTomasz P. RadonRoberto SalviaRita T. LawlorNicholas R. LemoineAldo ScarpaClaude ChelalaTatjana Crnogorac-JurcevicNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jun Wang Laurent Dumartin Andrea Mafficini Pinar Ulug Ajanthah Sangaralingam Namaa Audi Alamiry Tomasz P. Radon Roberto Salvia Rita T. Lawlor Nicholas R. Lemoine Aldo Scarpa Claude Chelala Tatjana Crnogorac-Jurcevic Splice variants as novel targets in pancreatic ductal adenocarcinoma
description	Abstract Despite a wealth of genomic information, a comprehensive alternative splicing (AS) analysis of pancreatic ductal adenocarcinoma (PDAC) has not been performed yet. In the present study, we assessed whole exome-based transcriptome and AS profiles of 43 pancreas tissues using Affymetrix exon array. The AS analysis of PDAC indicated on average two AS probe-sets (ranging from 1–28) in 1,354 significantly identified protein-coding genes, with skipped exon and alternative first exon being the most frequently utilised. In addition to overrepresented extracellular matrix (ECM)-receptor interaction and focal adhesion that were also seen in transcriptome differential expression (DE) analysis, Fc gamma receptor-mediated phagocytosis and axon guidance AS genes were also highly represented. Of note, the highest numbers of AS probe-sets were found in collagen genes, which encode the characteristically abundant stroma seen in PDAC. We also describe a set of 37 ‘hypersensitive’ genes which were frequently targeted by somatic mutations, copy number alterations, DE and AS, indicating their propensity for multidimensional regulation. We provide the most comprehensive overview of the AS landscape in PDAC with underlying changes in the spliceosomal machinery. We also collate a set of AS and DE genes encoding cell surface proteins, which present promising diagnostic and therapeutic targets in PDAC.
format	article
author	Jun Wang Laurent Dumartin Andrea Mafficini Pinar Ulug Ajanthah Sangaralingam Namaa Audi Alamiry Tomasz P. Radon Roberto Salvia Rita T. Lawlor Nicholas R. Lemoine Aldo Scarpa Claude Chelala Tatjana Crnogorac-Jurcevic
author_facet	Jun Wang Laurent Dumartin Andrea Mafficini Pinar Ulug Ajanthah Sangaralingam Namaa Audi Alamiry Tomasz P. Radon Roberto Salvia Rita T. Lawlor Nicholas R. Lemoine Aldo Scarpa Claude Chelala Tatjana Crnogorac-Jurcevic
author_sort	Jun Wang
title	Splice variants as novel targets in pancreatic ductal adenocarcinoma
title_short	Splice variants as novel targets in pancreatic ductal adenocarcinoma
title_full	Splice variants as novel targets in pancreatic ductal adenocarcinoma
title_fullStr	Splice variants as novel targets in pancreatic ductal adenocarcinoma
title_full_unstemmed	Splice variants as novel targets in pancreatic ductal adenocarcinoma
title_sort	splice variants as novel targets in pancreatic ductal adenocarcinoma
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5e296d11dc7c438894ef3382cb3a4a71
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Splice variants as novel targets in pancreatic ductal adenocarcinoma

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