TY - JOUR
T1 - Distinct epigenetic landscapes underlie the pathobiology of pancreatic cancer subtypes
AU - Lomberk, Gwen
AU - Blum, Yuna
AU - Nicolle, Rémy
AU - Nair, Asha
AU - Gaonkar, Krutika Satish
AU - Marisa, Laetitia
AU - Mathison, Angela
AU - Sun, Zhifu
AU - Yan, Huihuang
AU - Elarouci, Nabila
AU - Armenoult, Lucile
AU - Ayadi, Mira
AU - Ordog, Tamas
AU - Lee, Jeong Heon
AU - Oliver, Gavin
AU - Klee, Eric
AU - Moutardier, Vincent
AU - Gayet, Odile
AU - Bian, Benjamin
AU - Duconseil, Pauline
AU - Gilabert, Marine
AU - Bigonnet, Martin
AU - Garcia, Stephane
AU - Turrini, Olivier
AU - Delpero, Jean Robert
AU - Giovannini, Marc
AU - Grandval, Philippe
AU - Gasmi, Mohamed
AU - Secq, Veronique
AU - De Reyniès, Aurélien
AU - Dusetti, Nelson
AU - Iovanna, Juan
AU - Urrutia, Raul
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-018-04383-6
DO - 10.1038/s41467-018-04383-6
M3 - Article
C2 - 29773832
AN - SCOPUS:85047248746
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1978
ER -