Genomewide screening of DNA copy number changes in chronic myelogenous leukemia with the use of high-resolution array-based comparative genomic hybridization
Genomewide screening of DNA copy number changes in chronic myelogenous leukemia with the use of high-resolution array-based comparative genomic hybridization
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DOI：
10.1002/gcc.20303
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发表时间：
2006-05-01
影响因子：
3.7
通讯作者：
Ogawa, S
中科院分区：
文献类型：
--
作者：
Hosoya, N;Sanada, M;Ogawa, S
慢性粒细胞白血病(CML)由费城染色体特征的慢性期(CP)演变而来。如果没有有效的治疗，它会进展到加速阶段(AP)，并最终发展为致命的爆炸危机(BC)。为了确定与CML分期有关的基因，我们利用基于高分辨率阵列的比较基因组杂交(ARRAGE CGH)技术对55例不同阶段CML患者的DNA拷贝数变化进行了全基因组筛查。我们构建了包含3,151个细菌人工染色体(BAC)DNA的人类IM阵列，允许整个基因组的平均分辨率为1.0Mb。除了常见的染色体异常，阵列计算全息分析揭示了一些新的拷贝数变化。这些变化包括2q26.2-q37.3、5q23的损失。1-q23.3、5q31.2-q32、7p21.3-p11.2、7q31.1-q31.33、8pert-p12(p11.2)、9p和22q13.1-q13.31；3q26.2-q29、6p22.3、7p15.2-p14.3、8p12、8p21.3、8p23.2、8q24.13-q24.21、9q、19p13.2-p12和22q 13.1-q13.32出现频率较高。甚至影响单个BAC基因座的最小拷贝数变化也被识别出来。我们的数据表明，至少有一部分CML患者携带着仍然未知的隐蔽基因组改变，这些改变可能会影响CML疾病进展中的一个或多个重要基因。本文包含补充材料，可在http：//www.intercience.wiley.com/ipages/I 045-2257/suppmat上找到。(C)2006年Wiley-Liss，Inc.
Chronic myelogenous leukemia (CML) evolves from an indolent chronic phase (CP) characterized by the Philadelphia chromosome. Without effective therapy, it progresses to an accelerated phase (AP) and eventually to a fatal blast crisis (BC). To identify the genes involved in stage progression in CML, we performed a genomewide screening of DNA copy number changes in a total of 55 CML patients in different stages with the use of the high-resolution array-based comparative genomic hybridization (array CGH) technique. We constructed Human IM arrays that contained 3,151 bacterial artificial chromosome (BAC) DNAs, allowing for an average resolution of 1.0 Mb across the entire genome. In addition to common chromosomal abnormalities, array CGH analysis unveiled a number of novel copy number changes. These alterations included losses in 2q26.2-q37.3, 5q23. 1-q23.3, 5q31.2-q32, 7p21.3-p11.2,7q31.1-q31.33, 8pter-p12(p11.2), 9p, and 22q 13.1-q 13.31 and gains in 3q26.2-q29, 6p22.3, 7p15.2-p 14.3, 8p 12, 8p21.3, 8p23.2, 8q24.13-q24.21, 9q, 19p 13.2-p 12, and 22q 13.1-q 13.32 and occurred at a higher frequency in AP and BC. Minimal copy number changes affecting even a single BAC locus were also identified. Our data suggests that at least a proportion of CML patients carry still-unknown cryptic genomic alterations that could affect a gene or genes of importance in the disease progression of CML This article contains Supplementary Material available at http:// www.interscience.wiley.com/ipages/ I 045-2257/suppmat. (c) 2006 Wiley-Liss, Inc.