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Distinct epigenetic landscapes underlie the pathobiology of pancreatic cancer subtypes. Nat Commun 2018 05 17;9(1):1978

Date

05/19/2018

Pubmed ID

29773832

Pubmed Central ID

PMC5958058

DOI

10.1038/s41467-018-04383-6

Scopus ID

2-s2.0-85047248746   115 Citations

Abstract

Recent studies have offered ample insight into genome-wide expression patterns to define pancreatic ductal adenocarcinoma (PDAC) subtypes, although there remains a lack of knowledge regarding the underlying epigenomics of PDAC. Here we perform multi-parametric integrative analyses of chromatin immunoprecipitation-sequencing (ChIP-seq) on multiple histone modifications, RNA-sequencing (RNA-seq), and DNA methylation to define epigenomic landscapes for PDAC subtypes, which can predict their relative aggressiveness and survival. Moreover, we describe the state of promoters, enhancers, super-enhancers, euchromatic, and heterochromatic regions for each subtype. Further analyses indicate that the distinct epigenomic landscapes are regulated by different membrane-to-nucleus pathways. Inactivation of a basal-specific super-enhancer associated pathway reveals the existence of plasticity between subtypes. Thus, our study provides new insight into the epigenetic landscapes associated with the heterogeneity of PDAC, thereby increasing our mechanistic understanding of this disease, as well as offering potential new markers and therapeutic targets.

Author List

Lomberk G, Blum Y, Nicolle R, Nair A, Gaonkar KS, Marisa L, Mathison A, Sun Z, Yan H, Elarouci N, Armenoult L, Ayadi M, Ordog T, Lee JH, Oliver G, Klee E, Moutardier V, Gayet O, Bian B, Duconseil P, Gilabert M, Bigonnet M, Garcia S, Turrini O, Delpero JR, Giovannini M, Grandval P, Gasmi M, Secq V, De Reyni??s A, Dusetti N, Iovanna J, Urrutia R

Authors

Gwen Lomberk PhD Professor in the Surgery department at Medical College of Wisconsin
Angela Mathison PhD Assistant Professor in the Surgery department at Medical College of Wisconsin
Raul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Aged
Aged, 80 and over
Animals
Biomarkers, Tumor
Carcinoma, Pancreatic Ductal
Cell Line, Tumor
Chromatin Immunoprecipitation
DNA Methylation
Datasets as Topic
Epigenesis, Genetic
Female
Gene Expression Regulation, Neoplastic
Histones
Humans
Male
Mice
Mice, Nude
Middle Aged
Pancreatic Neoplasms
Regulatory Sequences, Nucleic Acid
Sequence Analysis, RNA
Xenograft Model Antitumor Assays