Department of Medicine, Hematology Oncology Division, Weill Cornell Medical College, New York, NY 10065, USA.
Cancer Cell. 2010 Jan 19;17(1):13-27. doi: 10.1016/j.ccr.2009.11.020. Epub 2010 Jan 7.
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).
我们假设，在癌细胞中，DNA 甲基化会呈现出特定的模式，这些模式反映了关键的生物学差异。因此，我们检测了 344 名急性髓系白血病 (AML) 患者的甲基化谱。对这些患者的甲基化数据进行聚类，将患者分为 16 组。其中 5 组定义了新的 AML 亚型，它们没有其他已知特征。此外，DNA 甲基化谱将 CEBPA 异常的患者与其他类型的白血病区分开来，定义了四种具有 NPM1 突变的表观遗传上不同形式的 AML，并表明已建立的 AML1-ETO、CBFb-MYH11 和 PML-RARA 白血病实体与特定的甲基化谱相关。我们报告了一个在独立患者队列中具有总体生存预测能力的 15 个基因甲基化分类器（p < 0.001，经已知协变量调整）。
