Human Gene Set: OHM_METHYLATED_IN_ADULT_CANCERS


Standard name OHM_METHYLATED_IN_ADULT_CANCERS
Systematic name M1233
Brief description Genes showing frequent DNA methylation and which are silenced in adult cancers but remain unmethylated in embryonic carcinoma and embryonic stem (ES) cells.
Full description or abstract Adult cancers may derive from stem or early progenitor cells. Epigenetic modulation of gene expression is essential for normal function of these early cells but is highly abnormal in cancers, which often show aberrant promoter CpG island hypermethylation and transcriptional silencing of tumor suppressor genes and pro-differentiation factors. We find that for such genes, both normal and malignant embryonic cells generally lack the hypermethylation of DNA found in adult cancers. In embryonic stem cells, these genes are held in a 'transcription-ready' state mediated by a 'bivalent' promoter chromatin pattern consisting of the repressive mark, histone H3 methylated at Lys27 (H3K27) by Polycomb group proteins, plus the active mark, methylated H3K4. However, embryonic carcinoma cells add two key repressive marks, dimethylated H3K9 and trimethylated H3K9, both associated with DNA hypermethylation in adult cancers. We hypothesize that cell chromatin patterns and transient silencing of these important regulatory genes in stem or progenitor cells may leave these genes vulnerable to aberrant DNA hypermethylation and heritable gene silencing during tumor initiation and progression.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17211412   Authors: Ohm JE,McGarvey KM,Yu X,Cheng L,Schuebel KE,Cope L,Mohammad HP,Chen W,Daniel VC,Yu W,Berman DM,Jenuwein T,Pruitt K,Sharkis SJ,Watkins DN,Herman JG,Baylin SB
Exact source Table 1S
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Source species Homo sapiens
Contributed by Leona Saunders (MSigDB Team)
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identifier namespace		 HUMAN_GENE_SYMBOL
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Version history 3.0: First introduced

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