Distinction in gene expression profiles of oligodendrogliomas with and without allelic loss of 1p
Distinction in gene expression profiles of oligodendrogliomas with and without allelic loss of 1p
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DOI：
10.1038/sj.onc.1205495
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发表时间：
2002-06-06
期刊：
影响因子：
8
通讯作者：
Aburatani, H
中科院分区：
文献类型：
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作者：
Mukasa, A;Ueki, K;Aburatani, H
少突胶质细胞瘤经常但并不总是表现出对化疗的敏感性，最近的研究表明，1p 染色体的等位基因丢失与这种化疗敏感性高度相关。为了深入了解这种差异的分子机制，我们使用寡核苷酸微阵列（GeneChip）检查了 11 种少突胶质细胞肿瘤（其中 6 种有 1pLOH，5 种没有 1pLOH（杂合性丢失））和两种正常脑组织的综合基因表达谱。统计上显着数量的基因在两个遗传亚群之间表达差异。聚类分析很好地分离了肿瘤亚群。对于那些差异表达的基因，具有 1pLOH 的肿瘤与正常大脑具有相似的表达谱。许多在 1pLOH 肿瘤中表现出较高表达的基因被认为在神经组织中具有功能。值得注意的是，在 1PLOH 肿瘤中表现出显着表达减少的 123 个基因中，大多数位于 1 号染色体上 (50%) 或 19 号染色体上 (10%)，平均表达减少率约为 50% (0.54 +/- 0.13)，可能反映了染色体缺失。因此，少突胶质细胞瘤遗传亚型之间的生物学差异确实反映在基因表达谱上，这为进一步研究阐明胶质瘤化疗敏感性机制提供了基线信息。
Oligodendrogliomas frequently, but not always show sensitivity to chemotherapy and recent studies demonstrated that allelic loss of chromosome 1p is highly associated with this chemosensitivity. To gain insight into the molecular mechanism of such difference, we examined comprehensive gene expression profiles of 11 oligodendroglial tumors, six with and five without 1pLOH (loss of heterozygosity), and two normal brain tissues using the oligonucleotide microarray (GeneChip). Statistically significant numbers of genes were expressed differentially between the two genetic subsets. Clustering analysis separated the tumor subsets well. The tumors with 1pLOH had similar expression profiles to the normal brain for those differentially expressed genes. Many genes showing higher expression in tumors with 1pLOH were presumed to have functions in nervous tissues. Notably, the majority of the 123 genes showing significant expression reduction in tumors with 1PLOH were either on chromosome 1 (50%) or on 19 (10%), and the average expression reduction ratio was about 50% (0.54 +/- 0.13) possibly reflecting the chromosomal deletion. Thus, the biological difference between the genetic subsets of oligodendroglioma was indeed reflected to gene expression profile, which provided baseline information for further studies to elucidate the mechanism of chemosensitivity in gliomas.