High-resolution mapping of amplifications and deletions in pediatric osteosarcoma by use of CGH analysis of cDNA microarrays
High-resolution mapping of amplifications and deletions in pediatric osteosarcoma by use of CGH analysis of cDNA microarrays
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DOI：
10.1002/gcc.10273
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发表时间：
2003-11-01
影响因子：
3.7
通讯作者：
Zielenska, M
中科院分区：
文献类型：
--
作者：
Squire, JA;Pei, JM;Zielenska, M
传统的细胞遗传学和比较基因组杂交（CGH）研究表明，骨肉瘤（OS）的特点是复杂的结构和数值染色体改变以及基因扩增。在这项研究中，我们使用高分辨率 CGH 来研究基因组失衡的复发模式，方法是使用来自 9 个 OS 肿瘤的 DNA 与 19,200 个克隆 cDNA 微阵列杂交。在六个操作系统中，存在 6p 的拷贝数增益或扩增，增益最小区域集中在片段 6p12.1 上。在七个 OS 中，影响染色体臂 8q 的扩增模式显示 8q 12-21.3 和 8q22-q23 的高水平增益，并且 MYC 癌基因在 8q24.2 处扩增。七个 OS 在 GAS7 和 PM1 (17p11.2-17p12) 边界的基因座之间显示出 17p 的拷贝数增加或扩增，其中三个肿瘤也在 17p13 处显示出小幅损失，包括含有 TP53 的区域。对该区域中节段重复（双倍子）分布的计算机分析识别出大量由映射到 17p 区域的旁系同源序列组成的区域，涵盖 OS 中的删除和扩增区域。有趣的是，在同一区域内存在双倍子簇和一些在骨形态发生和 CS 过程中表达的基因。总之，OS 染色体失衡的微阵列 CGH 分析证实了使用中期 CGH 观察到的总体模式，并更精确地细化了表征该肿瘤的基因组增益和损失的边界。 (C) 2003 Wiley-Liss, Inc.
Conventional cytogenetic and comparative genomic hybridization (CGH) studies have shown that osteosarcomas (OSs) are characterized by complex structural and numerical chromosomal alterations and gene amplification. In this study, we used high-resolution CGH to investigate recurrent patterns of genomic imbalance by use of DNA derived from nine OS tumors hybridized to a 19,200-clone cDNA microarray. In six OSs, there was copy number gain or amplification of 6p, with a minimal region of gain centering on segment 6p12.1. In seven OSs, the pattern of amplification affecting chromosome arm 8q showed high-level gains of 8q 12-21.3 and 8q22-q23, with amplification of the MYC oncogene at 8q24.2. Seven OSs showed copy number gain or amplification of 17p between the loci bounded by GAS7 and PM1 (17p11.2-17p12), and three of these tumors also showed small losses at 17p13, including the region containing TP53. An in silico analysis of the distribution of segmental duplications (duplicons) in this region identified a large number of tracts consisting of paralogous sequences mapping to the 17p region, encompassing the region of deletions and amplifications in OS. Interestingly, within this same region there were clusters of duplicons and several genes that are expressed during bone morphogenesis and in CS. In summary, microarray CGH analysis of the chromosomal imbalances of OS confirm the overall pattern observed by use of metaphase CGH and provides a more precise refinement of the boundaries of genomic gains and losses that characterize this tumor. (C) 2003 Wiley-Liss, Inc.