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

Details

Ressource 1Download: 30355485.pdf (3823.30 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_ADC19C98A2C8
Type
Article: article from journal or magazin.
Collection
Publications
Title
Pan-Cancer Landscape of Aberrant DNA Methylation across Human Tumors.
Journal
Cell reports
Author(s)
Saghafinia S., Mina M., Riggi N., Hanahan D., Ciriello G.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
23/10/2018
Peer-reviewed
Oui
Volume
25
Number
4
Pages
1066-1080.e8
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.
Keywords
DNA methylation instability, TCGA pan-cancer cohort, aberrant DNA methylation, cancer epigenetics, pediatric cancer
Pubmed
Web of science
Open Access
Yes
Create date
02/11/2018 8:46
Last modification date
20/08/2019 15:17
Usage data