Pan-Cancer Landscape of Aberrant DNA Methylation across Human Tumors.

Détails

Ressource 1Télécharger: 30355485.pdf (3823.30 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_ADC19C98A2C8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Pan-Cancer Landscape of Aberrant DNA Methylation across Human Tumors.
Périodique
Cell reports
Auteur(s)
Saghafinia S., Mina M., Riggi N., Hanahan D., Ciriello G.
ISSN
2211-1247 (Electronic)
Statut éditorial
Publié
Date de publication
23/10/2018
Peer-reviewed
Oui
Volume
25
Numéro
4
Pages
1066-1080.e8
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
The discovery of cancer-associated alterations has primarily focused on genetic variants. Nonetheless, altered epigenomes contribute to deregulate transcription and promote oncogenic pathways. Here, we designed an algorithmic approach (RESET) to identify aberrant DNA methylation and associated cis-transcriptional changes across >6,000 human tumors. Tumors exhibiting mutations of chromatin remodeling factors and Wnt signaling displayed DNA methylation instability, characterized by numerous hyper- and hypo-methylated loci. Most silenced and enhanced genes coalesced in specific pathways including apoptosis, DNA repair, and cell metabolism. Cancer-germline antigens (CG) were frequently epigenomically enhanced and their expression correlated with response to anti-PD-1, but not anti-CTLA4, in skin melanoma. Finally, we demonstrated the potential of our approach to explore DNA methylation changes in pediatric tumors, which frequently lack genetic drivers and exhibit epigenomic modifications. Our results provide a pan-cancer map of aberrant DNA methylation to inform functional and therapeutic studies.
Mots-clé
DNA methylation instability, TCGA pan-cancer cohort, aberrant DNA methylation, cancer epigenetics, pediatric cancer
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/11/2018 8:46
Dernière modification de la notice
20/08/2019 15:17
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