DNA Methylation Signatures Identify Biologically Distinct Subtypes in Acute Myeloid Leukemia

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2010 Jan 12

PMID 20060365

Citations 405

Authors

Maria E Figueroa

Sanne Lugthart

Yushan Li

Claudia Erpelinck-Verschueren

Xutao Deng

Paul J Christos

Elizabeth Schifano

James Booth

Wim van Putten

Lucy Skrabanek

Fabien Campagne

Madhu Mazumdar

John M Greally

Peter J M Valk

Bob Lowenberg

Ruud Delwel

Ari Melnick

Affiliations

Soon will be listed here.

Abstract

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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