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Genome-wide profiling of CpG methylation identifies novel targets of aberrant hypermethylation in myeloid leukemia.
- Source :
-
Cancer research [Cancer Res] 2006 Jun 15; Vol. 66 (12), pp. 6118-28. - Publication Year :
- 2006
-
Abstract
- The methylation of CpG islands is associated with transcriptional repression and, in cancer, leads to the abnormal silencing of tumor suppressor genes. Because aberrant hypermethylation may be used as a marker for disease, a sensitive method for the global detection of DNA methylation events is of particular importance. We describe a novel and robust technique, called methyl-CpG immunoprecipitation, which allows the unbiased genome-wide profiling of CpG methylation in limited DNA samples. The approach is based on a recombinant, antibody-like protein that efficiently binds native CpG-methylated DNA. In combination with CpG island microarrays, the technique was used to identify >100 genes with aberrantly methylated CpG islands in three myeloid leukemia cell lines. Interestingly, within all hypermethylation targets, genes involved in transcriptional regulation were significantly overrepresented. More than half of the identified genes were absent in microarray expression studies in either leukemia or normal monocytes, indicating that hypermethylation in cancer may be largely independent of the transcriptional status of the affected gene. Most individually tested genes were also hypermethylated in primary blast cells from acute myeloid leukemia patients, suggesting that our approach can identify novel potential disease markers. The technique may prove useful for genome-wide comparative methylation analysis not only in malignancies.
- Subjects :
- Acute Disease
Cell Line, Tumor
DNA, Neoplasm genetics
DNA, Neoplasm metabolism
Gene Expression Profiling
Genome, Human
Humans
Immunoglobulin Fragments chemistry
Immunoglobulin Fragments genetics
Immunoglobulin Fragments immunology
Immunoprecipitation methods
Leukemia, Myeloid metabolism
Oligonucleotide Array Sequence Analysis
Polymerase Chain Reaction
Promoter Regions, Genetic
RNA, Messenger biosynthesis
RNA, Messenger genetics
Recombinant Fusion Proteins chemistry
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins immunology
Reproducibility of Results
U937 Cells
CpG Islands genetics
DNA Methylation
Leukemia, Myeloid genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0008-5472
- Volume :
- 66
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 16778185
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-06-0376