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Pan-Cancer Landscape of Aberrant DNA Methylation across Human Tumors
- Source :
- Cell Reports, Vol 25, Iss 4, Pp 1066-1080.e8 (2018), Cell reports, vol. 25, no. 4, pp. 1066-1080.e8
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Summary: 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. : Saghafinia et al. present an algorithmic approach to identify cancer-associated DNA methylation changes affecting gene expression. By analyzing >6,000 adult and pediatric tumors, the authors identify numerous DNA methylation changes at gene promoters that coalesce into a few pathways and that were associated with patient prognosis and response to therapy. Keywords: aberrant DNA methylation, cancer epigenetics, DNA methylation instability, TCGA pan-cancer cohort, pediatric cancer
- Subjects :
- 0301 basic medicine
DNA repair
hepatocellular-carcinoma
promoter methylation
wilms-tumor
Biology
General Biochemistry, Genetics and Molecular Biology
Chromatin remodeling
Epigenesis, Genetic
03 medical and health sciences
Cell Line, Tumor
Neoplasms
nf-kappa-b
expression
Humans
Gene Silencing
Cancer epigenetics
gene
Child
lcsh:QH301-705.5
Gene
Epigenomics
Wnt signaling pathway
genomic characterization
DNA Methylation
DNA methylation instability
TCGA pan-cancer cohort
aberrant DNA methylation
cancer epigenetics
pediatric cancer
Pediatric cancer
signaling pathways
3. Good health
comprehensive molecular characterization
030104 developmental biology
lcsh:Biology (General)
DNA methylation
Cancer research
metastatic melanoma
Subjects
Details
- ISSN :
- 22111247
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....850d6a60a1d9e4746425a33f6a3db0e6