| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Biology, Pathobiology, and Genetics |
1 Institute for Cancer Genetics, 2 Genome Center, and 3 Department of Pathology, Columbia University Medical Center; 4 New York State Psychiatric Institute, New York, New York and 5 Department of Laboratory Medicine and Hematology and 6 Department of Medicine and Leukemia Unit, Ontario Cancer Institute and University of Toronto, Toronto, Ontario, Canada
Requests for reprints: Benjamin Tycko, Institute for Cancer Genetics, Columbia University Medical Center, 1150 St. Nicholas Avenue, New York, NY 10032. Phone: 212-305-1149; Fax: 212-305-5489; E-mail: bt12{at}columbia.edu.
Progress on several unresolved issues in cancer epigenetics will benefit from rapid and standardized methods for profiling DNA methylation genome-wide. In the area of epigenetic therapy, the demethylating drug decitabine (5-aza-2'-deoxycytidine) is increasingly used to treat acute myelogenous leukemia and myelodysplastic syndrome, but the mechanisms of its anticancer activity have remained unclear. Given the clinical efficacy of decitabine and the uncertainties about its mode of action, it will be useful to optimize methods for following DNA methylation as a biochemical response in individual patients. Here, we describe a single nucleotide polymorphism (SNP) chip-based method (MSNP) for profiling DNA methylation. Using this procedure, the extent of demethylation in bone marrow aspirates from patients with leukemia receiving decitabine can be assessed genome-wide using commercially available (Affymetrix) SNP chips. We validated the accuracy of MSNP by comparing the results with combined bisulfite restriction analysis and by sequencing cloned PCR products from bisulfite-converted DNA. We further validated MSNP in a Wilms' tumor/normal kidney comparison, comparing the results with methylation-sensitive Southern blotting. MSNP simultaneously detects aberrations in DNA copy number and loss of heterozygosity, making it a generally useful approach for combined genetic and epigenetic profiling in tissue samples from cancer patients. (Cancer Res 2006; 66(7): 3443-51)
This article has been cited by other articles:
|
|
 |
|
  M. Oda, J. L. Glass, R. F. Thompson, Y. Mo, E. N. Olivier, M. E. Figueroa, R. R. Selzer, T. A. Richmond, X. Zhang, L. Dannenberg, et al. High-resolution genome-wide cytosine methylation profiling with simultaneous copy number analysis and optimization for limited cell numbers Nucleic Acids Res., April 22, 2009; (2009) gkp260v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Wouters, B. Lowenberg, and R. Delwel A decade of genome-wide gene expression profiling in acute myeloid leukemia: flashback and prospects Blood, January 8, 2009; 113(2): 291 - 298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Jiang, T. A. Gonda, M. V. Gamble, M. Salas, V. Seshan, S. Tu, W. S. Twaddell, P. Hegyi, G. Lazar, I. Steele, et al. Global Hypomethylation of Genomic DNA in Cancer-Associated Myofibroblasts Cancer Res., December 1, 2008; 68(23): 9900 - 9908. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Zilberman and S. Henikoff Genome-wide analysis of DNA methylation patterns Development, November 15, 2007; 134(22): 3959 - 3965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dubey and C. A. Powell Update in Lung Cancer 2006 Am. J. Respir. Crit. Care Med., May 1, 2007; 175(9): 868 - 874. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hellman and A. Chess Gene Body-Specific Methylation on the Active X Chromosome Science, February 23, 2007; 315(5815): 1141 - 1143. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
