DNA Methylation Signatures Identify Biologically Distinct Subtypes in Acute Myeloid Leukemia

被引：717

作者：

Figueroa, Maria E. ^{[2
]}

Lugthart, Sanne ^{[1
]}

Li, Yushan ^{[2
]}

Erpelinck-Verschueren, Claudia ^{[1
]}

Deng, Xutao ^{[3
]}

Christos, Paul J. ^{[4
]}

Schifano, Elizabeth ^{[7
]}

Booth, James ^{[7
]}

van Putten, Wim ^{[6
]}

Skrabanek, Lucy ^{[3
,5
]}

Campagne, Fabien ^{[3
,5
]}

Mazumdar, Madhu ^{[4
]}

Greally, John M. ^{[8
]}

Valk, Peter J. M. ^{[1
]}

Lowenberg, Bob ^{[1
]}

Delwel, Ruud ^{[1
]}

Melnick, Ari ^{[2
]}

机构：

[1] Erasmus Univ, Med Ctr, Dept Hematol, NL-3000 CA Rotterdam, Netherlands

[2] Weill Cornell Med Coll, Dept Med, Div Hematol Oncol, New York, NY 10065 USA

[3] Weill Cornell Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10065 USA

[4] Weill Cornell Med Coll, Dept Biostat & Epidemiol, New York, NY 10065 USA

[5] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10065 USA

[6] Erasmus Univ, Med Ctr, Dept Trials & Stat, NL-3000 CA Rotterdam, Netherlands

[7] Cornell Univ, Ithaca, NY 14853 USA

[8] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA

来源：

CANCER CELL | 2010年 / 17卷 / 01期

基金：

美国国家卫生研究院;

关键词：

GENE-EXPRESSION PROFILES; CYTOSINE METHYLATION; POOR-PROGNOSIS; P15(INK4B); MUTATIONS; BINDING; CEBPA; HELP;

D O I：

10.1016/j.ccr.2009.11.020

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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).

引用

页码：13 / 27

页数：15

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