High-resolution whole genome tiling path array CGH analysis of CD34+ cells from patients with low-risk myelodysplastic syndromes reveals cryptic copy number alterations and predicts overall and leukemia-free survival
High-resolution whole genome tiling path array CGH analysis of CD34+ cells from patients with low-risk myelodysplastic syndromes reveals cryptic copy number alterations and predicts overall and leukemia-free survival
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DOI：
10.1182/blood-2007-11-122028
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发表时间：
2008-10-15
期刊：
影响因子：
20.3
通讯作者：
Karsan, Aly
中科院分区：
文献类型：
--
作者：
Starczynowski, Daniel T.;Vercauteren, Suzanne;Karsan, Aly
骨髓增生异常综合征（MDS）由于遗传异质性和对疾病生物学知之甚少，构成了重要的诊断和治疗挑战。为了研究低危MDS患者的起始基因组改变和潜在的潜在预后意义，我们对44例国际预后评分系统评分小于或等于1.0的患者的CD 34（+）细胞进行了全基因组平铺路径阵列比较基因组杂交（aCGH）。在44名患者中的36名患者的细胞中检测到克隆拷贝数差异。相比之下，44名患者中只有16名患者的细胞显示核型异常。虽然大多数患者的核型正常，aCGH确定了21个重复的拷贝数改变。频繁的隐性改变的例子包括11q24.2-qter、17q11.2和17 q12的增加和2q33.1-q33.2、5q13.1-q13.2和10q21.3的损失。基因组完整性的维持定义为小于3 Mb的基因组总破坏与更好的总生存率相关（P = 0.002），与急性髓性白血病转化相关的频率较低（P = 0.033）。这项研究表明，在MDS患者的临床检查中使用aCGH的潜在作用。
Myelodysplastic syndromes (MDSs) pose an important diagnostic and treatment challenge because of the genetic heterogeneity and poorly understood biology of the disease. To investigate initiating genomic alterations and the potential prognostic significance of cryptic genomic changes in low-risk MDS, we performed whole genome tiling path array comparative genomic hybridization (aCGH) on CD34(+) cells from 44 patients with an International Prognostic Scoring System score less than or equal to 1.0. Clonal copy number differences were detected in cells from 36 of 44 patients. In contrast, cells from only 16 of the 44 patients displayed karyotypic abnormalities. Although most patients had normal karyotype, aCGH identified 21 recurring copy number alterations. Examples of frequent cryptic alterations included gains at 11q24.2-qter, 17q11.2, and 17q12 and losses at 2q33.1-q33.2, 5q13.1-q13.2, and 10q21.3. Maintenance of genomic integrity defined as less than 3 Mb total disruption of the genome correlated with better overall survival (P = .002) and was less frequently associated with transformation to acute myeloid leukemia (P = .033). This study suggests a potential role for the use of aCGH in the clinical workup of MDS patients.