Combined high-resolution array-based comparative genomic hybridization and expression profiling of ETV6/RUNX1-positive acute lymphoblastic leukemias reveal a high incidence of cryptic Xq duplications and identify several putative target genes within the commonly gained region
Combined high-resolution array-based comparative genomic hybridization and expression profiling of ETV6/RUNX1-positive acute lymphoblastic leukemias reveal a high incidence of cryptic Xq duplications and identify several putative target genes within the commonly gained region
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DOI：
10.1038/sj.leu.2404879
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发表时间：
2007-10-01
期刊：
影响因子：
11.4
通讯作者：
Fioretos, T.
中科院分区：
文献类型：
--
作者：
Lilljebjorn, H.;Heidenblad, M.;Fioretos, T.
采用高分辨率阵列比较基因组杂交（array CGH）、基因表达谱分析和荧光原位杂交技术对17例ETV 6/RUNX 1阳性的儿童急性淋巴细胞白血病进行了研究。比较阵列CGH和基因表达模式显示，基因组失衡对受影响区域的基因表达产生了很大影响。阵列CGH分析鉴定了高频率的细胞遗传学隐性遗传变化，例如del（9 p）和del（12 p）。有趣的是，在11名男性中有6名（55%）发现了Xq材料的重复，大小在30和60 Mb之间变化，但在女性中没有发现。发现Xq上的基因在dup（Xq）病例中具有高表达水平;在外部基因表达数据集中，在t（12;21）阳性病例中证实了类似的过表达。通过研究最小获得区域中基因的表达谱和预期功能，鉴定了几个候选靶基因（SPAN XB、HMG B3、FAM 50 A、HTATSF 1和RAP 2C）。其中，睾丸特异性的斯潘XB基因是唯一一个显示高和均匀的过度表达，无论性别和Xq重复的存在，这表明该基因在t（12;21）阳性白血病中起重要的发病作用。
Seventeen ETV6/RUNX1-positive pediatric acute lymphoblastic leukemias were investigated by high-resolution array-based comparative genomic hybridization ( array CGH), gene expression profiling and fluorescence in situ hybridization. Comparing the array CGH and gene expression patterns revealed that genomic imbalances conferred a great impact on the expression of genes in the affected regions. The array CGH analyses identified a high frequency of cytogenetically cryptic genetic changes, for example, del(9p) and del(12p). Interestingly, a duplication of Xq material, varying between 30 and 60Mb in size, was found in 6 of 11 males (55%), but not in females. Genes on Xq were found to have a high expression level in cases with dup(Xq); a similar overexpression was confirmed in t(12;21)-positive cases in an external gene expression data set. By studying the expression profile and the proposed function of genes in the minimally gained region, several candidate target genes (SPANXB, HMGB3, FAM50A, HTATSF1 and RAP2C) were identified. Among them, the testis-specific SPANXB gene was the only one showing a high and uniform overexpression, irrespective of gender and presence of Xq duplication, suggesting that this gene plays an important pathogenetic role in t(12;21)-positive leukemia.