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 DuconseilMarine Gilabert, Martin Bigonnet, Stephane Garcia, Olivier Turrini, Jean Robert Delpero, Marc Giovannini, Philippe Grandval, Mohamed Gasmi, Veronique Secq, Aurélien De Reyniès, Nelson Dusetti, Juan Iovanna, Raul Urrutia

Research output: Contribution to journalArticle

34 Scopus 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.

Original languageEnglish (US)
Article number1978
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Lomberk, G., Blum, Y., Nicolle, R., Nair, A., Gaonkar, K. S., Marisa, L., Mathison, A., Sun, Z., Yan, H., Elarouci, N., Armenoult, L., Ayadi, M., Ordog, T., Lee, J. H., Oliver, G., Klee, E., Moutardier, V., Gayet, O., Bian, B., ... Urrutia, R. (2018). Distinct epigenetic landscapes underlie the pathobiology of pancreatic cancer subtypes. Nature communications, 9(1), [1978]. https://doi.org/10.1038/s41467-018-04383-6