Comprehensive characterisation of compartment-specific long non-coding RNAs associated with pancreatic ductal adenocarcinoma.
Carcinoma, Pancreatic Ductal
/ genetics
Computational Biology
/ methods
DNA Copy Number Variations
Gene Expression Profiling
/ methods
Gene Expression Regulation, Neoplastic
Genetic Markers
/ genetics
Germ-Line Mutation
High-Throughput Nucleotide Sequencing
/ methods
Humans
Kaplan-Meier Estimate
Pancreatic Neoplasms
/ genetics
Polymorphism, Single Nucleotide
Prognosis
RNA, Long Noncoding
/ genetics
RNA, Neoplasm
/ genetics
Transcriptome
RNA expression
cancer genetics
epithelial cells
gene regulation
pancreatic cancer
Journal
Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
19
04
2017
revised:
22
12
2017
accepted:
01
01
2018
pubmed:
15
2
2018
medline:
14
7
2020
entrez:
15
2
2018
Statut:
ppublish
Résumé
Pancreatic ductal adenocarcinoma (PDA) is a highly metastatic disease with limited therapeutic options. Genome and transcriptome analyses have identified signalling pathways and cancer driver genes with implications in patient stratification and targeted therapy. However, these analyses were performed in bulk samples and focused on coding genes, which represent a small fraction of the genome. We developed a computational framework to reconstruct the non-coding transcriptome from cross-sectional RNA-Seq, integrating somatic copy number alterations (SCNA), common germline variants associated to PDA risk and clinical outcome. We validated the results in an independent cohort of paired epithelial and stromal RNA-Seq derived from laser capture microdissected human pancreatic tumours, allowing us to annotate the compartment specificity of their expression. We employed systems and experimental biology approaches to interrogate the function of epithelial long non-coding RNAs (lncRNAs) associated with genetic traits and clinical outcome in PDA. We generated a catalogue of PDA-associated lncRNAs. We showed that lncRNAs define molecular subtypes with biological and clinical significance. We identified lncRNAs in genomic regions with SCNA and single nucleotide polymorphisms associated with lifetime risk of PDA and associated with clinical outcome using genomic and clinical data in PDA. Systems biology and experimental functional analysis of two epithelial lncRNAs ( Our findings indicate that lncRNAs are associated with genetic marks of pancreatic cancer risk, contribute to the transcriptional regulation of neoplastic cells and provide an important resource to design functional studies of lncRNAs in PDA.
Identifiants
pubmed: 29440233
pii: gutjnl-2017-314353
doi: 10.1136/gutjnl-2017-314353
pmc: PMC6086768
mid: NIHMS955934
doi:
Substances chimiques
Genetic Markers
0
RNA, Long Noncoding
0
RNA, Neoplasm
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
499-511Subventions
Organisme : NCI NIH HHS
ID : U54 CA209997
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA188059
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA193313
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA013696
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217858
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK063608
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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