Journal
CANCER CELL
Volume 17, Issue 1, Pages 13-27Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2009.11.020
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Funding
- National Institutes of Health [CA118316, R01 HD044078]
- Dutch Cancer Society [EMCR 2006-3522]
- EHA
- ZonMW
- SASS Foundation
- ASH
- NCI [R01 CA104348]
- Chemotherapy Foundation
- Sam Waxman Cancer Research Foundation
- GP Foundation
- Leukemia and Lymphoma Society
- Institutional Clinical and Translational Science [RFA-RM-07-002]
- NSF
- Clinical Translational Science Center (CTSC) [UL1-RR024996]
- [NSF-DMS 085865]
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We hypothesized that DNA methylation distributes into specific patterns in cancer cells, which reflect critical biological differences. We therefore examined the methylation profiles of 344 patients with acute myeloid leukemia (AML). Clustering of these patients by methylation data segregated patients into 16 groups. Five of these groups defined new AML subtypes that shared no other known feature. In addition, DNA methylation profiles segregated patients with CEBPA aberrations from other subtypes of leukemia, defined four epigenetically distinct forms of AML with NPM1 mutations, and showed that established AML1-ETO, CBFb-MYH11, and PML-RARA leukemia entities are associated with specific methylation profiles. We report a 15 gene methylation classifier predictive of overall survival in an independent patient cohort (p < 0.001, adjusted for known covariates).
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