Oct 5, 2001

Susceptibility of nonpromoter CpG islands to de novo methylation in normal and neoplastic cells

Journal of the National Cancer Institute
C T NguyenPeter A Jones


Many cancers display alterations in methylation patterns of CpG islands--stretches of DNA rich in CpG dinucleotides often associated with gene promoters that are involved in initiation of gene transcription. This methylation may perturb expression of genes critical to the regulation of cell proliferation. Aberrant methylation is not limited to a few genes or to promoter regions but has been found on a genome-wide scale in a variety of neoplasias, including colorectal cancer and acute myelogenous leukemia. Our goal was to characterize, in a quantitative manner, the profiles of abnormally methylated genes that may be specific for different cancers. Using a quantitative assay, methylation-sensitive single nucleotide primer extension (MS-SNuPE), we have analyzed the methylation levels of promoter and exonic (coding region) CpG islands of two cyclin-dependent kinase inhibitors [p15(INK4B) and p16(INK4A)] and the PAX6 gene, which encodes a transcriptional factor involved in neuronal proliferation, in DNA samples taken from patients with chronic myelogenous leukemia, acute myelogenous leukemia, myelodysplastic syndrome, and colorectal cancer. De novo methylation of all three exonic loci in tumors--relative to baseline levels found in ...Continue Reading

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Mentioned in this Paper

Cyclin-Dependent Kinase Inhibitor Proteins
Hematology (Discipline)
Leukemia, Myeloid, Chronic-Phase
Cell Cycle Proteins
Protein Methylation
Primer Extension
Neoplastic Cell
Metastasis Suppressor Genes
Cyclin-Dependent Kinase Inhibitor p16
Cell Proliferation Regulatory Process

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