Whole-genome profiling of chromosomal aberrations in hepatoblastoma using high-density single-nucleotide polymorphism genotyping microarrays
Whole-genome profiling of chromosomal aberrations in hepatoblastoma using high-density single-nucleotide polymorphism genotyping microarrays
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DOI：
10.1111/j.1349-7006.2007.00710.x
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发表时间：
2008-03-01
期刊：
影响因子：
5.7
通讯作者：
Hayashi, Yasuhide
中科院分区：
文献类型：
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作者：
Suzuki, Makoto;Kato, Motohiro;Hayashi, Yasuhide
为了确定肝母细胞瘤（HBL）（最常见的儿科肝脏肿瘤）的基因组谱并阐明其发病机制，我们对17个HBL样本进行了高密度全基因组单核苷酸多态性（SNP）微阵列分析。用于GeneChip（R）（CNAG）的拷贝数分析仪和使用匿名参考（AsCNAR）算法的等位基因特异性拷贝数分析使得能够在不使用配对正常DNA的情况下简单但灵敏地推断等位基因组成。染色体畸变15例（88%）。染色体1q、2（或2q）、8、17 q和20的增加以及染色体4q和11 q的丢失经常被鉴定。在7q34、14q11.2和11q22.2检测到高级别扩增。除纯合缺失外，还鉴定了几种类型的缺失。最重要的是，在17个HBL样本中的4个中检测到11p15处的拷贝中性杂合性丢失（单亲二体性[UPD]）。胰岛素样生长因子II（IGF2）和H19基因位于该区域内。该区域的甲基化状态表明UPD的父系起源。IGF2和H19基因在UPD组和非UPD组中的表达模式相反。这种表达模式的差异可能会影响HBL的临床特征。
To identify the genomic profile and elucidate the pathogenesis of hepatoblastoma (HBL), the most common pediatric hepatic tumor, we performed high-density genome-wide single-nucleotide polymorphism (SNP) microarray analyses of 17 HBL samples. The copy number analyzer for GeneChip (R) (CNAG) and allele-specific copy number analysis using anonymous references (AsCNAR) algorithms enabled simple but sensitive inference of allelic composition without using paired normal DNA. Chromosomal aberrations were observed in 15 cases (88%). Gains in chromosomes 1q, 2 (or 2q), 8, 17q, and 20 and losses in chromosomes 4q and 11q were frequently identified. High-grade amplifications were detected at 7q34, 14q11.2, and 11q22.2. Several types of deletions, except homozygous deletion, were identified. Most importantly, copy-neutral loss of heterozygosity (uniparental disomy [UPD]) at 11p15 was detected in four of the 17 HBL samples. Insulin-like growth factor II (IGF2) and H19 genes were located within this region. The methylated status of this region indicated the paternal origin of the UPD. The expression patterns of IGF2 and H19 were opposite between genes with and without the UPD. This difference in the expression patterns might influence the clinical features of HBL.