Distinct epigenetic landscapes underlie the pathobiology of pancreatic cancer subtypes. Nat Commun 2018 May 17;9(1):1978
Date
05/19/2018Pubmed ID
29773832Pubmed Central ID
PMC5958058DOI
10.1038/s41467-018-04383-6Scopus ID
2-s2.0-85047248746 (requires institutional sign-in at Scopus site) 157 CitationsAbstract
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 Reyniès A, Dusetti N, Iovanna J, Urrutia RAuthors
Gwen Lomberk PhD Professor in the Surgery department at Medical College of WisconsinAngela 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
AgedAged, 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
