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DNA hypermethylation accompanied by transcriptional repression in follicular lymphoma
- Source :
- Genes, Chromosomes and Cancer. 48:828-841
- Publication Year :
- 2009
- Publisher :
- Wiley, 2009.
-
Abstract
- High-throughput microarray technologies were used to study DNA methylation accompanied by transcriptional changes in follicular lymphoma (FL). Using Methylated CpG Island Amplification with Microarrays (MCAM) to study CpG Island (CGI) DNA methylation in follicular lymphoma (FL) we discovered widespread hypermethylation of homeobox genes and previously identified targets of polycomb repressive complex 2 (PRC2) in cell lines and primary tumors, but not in benign follicular hyperplasia (BFH). DNA methylation for HOXA11, HOXD10, HOXB7, HOXC12, PAX6, LHX9, SFMBT2, EN2 and PAX7 was independently validated in the RL cell line and HOXA11, HOXD10, PAX6 and EN2 in primary tumors. Combined Bisulfite Restriction Analysis (COBRA) also established DNA methylation for the previously identified PRC2 targets DCC, DES, GAD2, AQP5, GPR61, GRIA4, GJD2 and AMPH in FL but not in BFH. Gene expression analyses revealed 411 genes that were hypermethylated and transcriptionally repressed in RL, 74% of which were re-activated by the demethylating agent 5-aza-2′-deoxycytidine (5-azaD) plus or minus the histone deacetylase inhibitor trichostatin A (TSA). Forty genes were also down-regulated in primary FL. Our results suggest that extensive hypermethylation in promoters of polycomb target genes is a characteristic of FL and that loss of expression of certain SUZ12 target genes could be functionally relevant for lymphomagenesis.
- Subjects :
- Male
Cancer Research
Transcription, Genetic
Polycomb-Group Proteins
Biology
Article
Epigenesis, Genetic
chemistry.chemical_compound
Cell Line, Tumor
Combined bisulfite restriction analysis
Genetics
medicine
SUZ12
Cluster Analysis
Humans
Cyclin D1
Promoter Regions, Genetic
Lymphoma, Follicular
Oligonucleotide Array Sequence Analysis
Homeodomain Proteins
Hyperplasia
Genes, Homeobox
Polycomb Repressive Complex 2
Nuclear Proteins
Reproducibility of Results
Promoter
DNA Methylation
Middle Aged
Molecular biology
Neoplasm Proteins
Demethylating agent
Repressor Proteins
Trichostatin A
CpG site
chemistry
DNA methylation
Cancer research
CpG Islands
Female
Lymph Nodes
Carrier Proteins
HOXD10
Transcription Factors
medicine.drug
Subjects
Details
- ISSN :
- 10982264 and 10452257
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- Genes, Chromosomes and Cancer
- Accession number :
- edsair.doi.dedup.....34c84a73c26f9d5ad6f6c323263a6f71