Distinct epigenetic landscapes underlie the pathobiology of pancreatic cancer subtypes

Gwen Lomberk (), Yuna Blum, Rémy Nicolle, Asha Nair, Krutika Satish Gaonkar, Laetitia Marisa, Angela Mathison, Zhifu Sun, Huihuang Yan, Nabila Elarouci, Lucile Armenoult, Mira Ayadi, Tamas Ordog, Jeong-Heon Lee, Gavin Oliver, Eric Klee, Vincent Moutardier, Odile Gayet, Benjamin Bian, Pauline Duconseil, Marine Gilabert, Martin Bigonnet, Stephane Garcia, Olivier Turrini, Jean-Robert Delpero, Marc Giovannini, Philippe Grandval, Mohamed Gasmi, Veronique Secq, Aurélien Reyniès, Nelson Dusetti, Juan Iovanna () and Raul Urrutia ()
Additional contact information
Gwen Lomberk: Medical College of Wisconsin
Yuna Blum: Ligue Nationale Contre Le Cancer
Rémy Nicolle: Ligue Nationale Contre Le Cancer
Asha Nair: Mayo Clinic
Krutika Satish Gaonkar: Mayo Clinic
Laetitia Marisa: Ligue Nationale Contre Le Cancer
Angela Mathison: Medical College of Wisconsin
Zhifu Sun: Mayo Clinic
Huihuang Yan: Mayo Clinic
Nabila Elarouci: Ligue Nationale Contre Le Cancer
Lucile Armenoult: Ligue Nationale Contre Le Cancer
Mira Ayadi: Ligue Nationale Contre Le Cancer
Tamas Ordog: Mayo Clinic
Jeong-Heon Lee: Mayo Clinic
Gavin Oliver: Mayo Clinic
Eric Klee: Mayo Clinic
Vincent Moutardier: Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy
Odile Gayet: Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy
Benjamin Bian: Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy
Pauline Duconseil: Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy
Marine Gilabert: Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy
Martin Bigonnet: Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy
Stephane Garcia: Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy
Olivier Turrini: Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy
Jean-Robert Delpero: Institut Paoli-Calmettes
Marc Giovannini: Institut Paoli-Calmettes
Philippe Grandval: Hôpital de la Timone
Mohamed Gasmi: Hôpital Nord, Chemin des Bourrely
Veronique Secq: Hôpital Nord, Chemin des Bourrely
Aurélien Reyniès: Ligue Nationale Contre Le Cancer
Nelson Dusetti: Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy
Juan Iovanna: Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy
Raul Urrutia: Medical College of Wisconsin

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04383-6

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