Integration of Genomic and Gene Expression Data of Childhood ALL Without Known Aberrations Identifies Subgroups with Specific Genetic Hallmarks
Integration of Genomic and Gene Expression Data of Childhood ALL Without Known Aberrations Identifies Subgroups with Specific Genetic Hallmarks
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DOI：
10.1002/gcc.20616
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发表时间：
2009-01-01
影响因子：
3.7
通讯作者：
Cazzaniga, Giovanni
中科院分区：
文献类型：
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作者：
Bungaro, Silvia;Dell'Orto, Marta Campo;Cazzaniga, Giovanni
儿童急性淋巴细胞白血病(ALL)包括遗传上不同的亚型。然而，25%的病例仍然缺乏明确的遗传特征。为了确定常规方法无法分类的儿童ALL患者的基因组异常，我们对29例患者的白血病细胞进行了基于单核苷酸多态(SNP)阵列的基因组分析。绝大多数病例(19/24，79%)显示出基因组异常；其中至少有一例影响了参与细胞周期调节或B细胞发育的基因。最相关的异常是CDKN2A/9p21缺失(7/24，29%)、ETV6(Tel)/12p13缺失(3/24，12%)和21号染色体染色体内扩增(IAMP21)(3/24，12%)。为了确定受反复发生的基因组改变直接或间接影响的基因表达的差异，我们整合了由相同样本的微阵列分析产生的基因组和基因表达数据。在CDKN2A纯合子缺失病例中，Smad1基因表达下调。JAG1基因编码Notch受体的锯齿状I配体，是ETV6缺失病例中差异表达(上调)基因之一。我们的研究结果表明，基因组分析和基因表达谱分析的结合可以识别常规方法未发现的遗传损伤，以及参与B-祖细胞ALL发病的潜在新途径。(C)2008年Wiley-Liss，Inc.
Pediatric acute lymphoblastic leukemia (ALL) comprises genetically distinct subtypes. However, 25% of cases still lack defined genetic hallmarks. To identify genomic aberrancies in childhood ALL patients nonclassifiable by conventional methods, we performed a single nuclecitide polymorphisms (SNP) array-based genomic analysis of leukemic cells from 29 cases. The vast majority of cases analyzed (19/24, 79%) showed genomic abnormalities; at least one of them affected either genes involved in cell cycle regulation or in B-cell development. The most relevant abnormalities were CDKN2A/9p21 deletions (7/24, 29%), ETV6 (TEL)/12p 13 deletions (3/24, 12%), and intrachromosomal amplifications of chromosome 21 (iAMP21) (3/24, 12%). To identify variation in expression of genes directly or indirectly affected by recurrent genomic alterations, we integrated genomic and gene expression data generated by microarray analyses of the same samples. SMAD 1 emerged as a down-regulated gene in CDKN2A homozygous deleted cases compared with nondeleted. The JAG1 gene, encoding the jagged I ligand of the Notch receptor, was among a list of differentially expressed (up-regulated) genes in ETV6-deleted cases. Our findings demonstrate that integration of genomic analysis and gene expression profiling can identify genetic lesions undetected by routine methods and potential novel pathways involved in B-progenitor ALL pathogenesis. (C) 2008 Wiley-Liss, Inc.