Integrated analysis of mutations, miRNA and mRNA expression in glioblastoma.
Integrated analysis of mutations, miRNA and mRNA expression in glioblastoma.
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DOI：
10.1186/1752-0509-4-163
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发表时间：
2010-11-29
影响因子：
--
通讯作者：
Xiong M
中科院分区：
文献类型：
--
作者：
Dong H;Luo L;Hong S;Siu H;Xiao Y;Jin L;Chen R;Xiong M
胶质母细胞瘤起源于多种遗传改变和环境扰动之间复杂的相互作用。很少有人关注遗传变异、基因表达改变和microRNA （miRNA）表达如何整合到网络中，这些网络共同作用改变调控，最终导致复杂表型和胶质母细胞瘤的出现。我们鉴定出14个基因的体细胞突变与胶质母细胞瘤相关，其中8个基因为新发现的；鉴定出11个基因的杂合缺失（LOH）与胶质母细胞瘤相关，其中9个基因为新发现的。通过基因共表达网络分析，我们确定了15个对网络功能至关重要的基因，其中大部分是癌症相关基因。我们还构建了miRNA共表达网络，发现19个重要的miRNA，其中3个与胶质母细胞瘤患者的生存有显著关系。我们确定了3,953对预测的miRNA-mRNA对，其中14对先前在其他组的实验中得到了验证。通过通路富集分析，我们还发现前19位重要mirna靶网络中的基因主要参与癌症相关的信号通路、突触传递和神经系统过程。最后，我们开发了新的方法来破译连接突变、表达信息和胶质母细胞瘤的途径。我们鉴定出4个顺式表达的数量性状位点（eQTL）： TP53、EGFR、NF1和PIK3C2G；262个反式eQTL和26个反式miRNA eQTL；2顺式eqtl: NRAP和EGFR；409个反式eQTL和27个反式miRNA eQTL用于杂合性缺失（LOH）突变。我们的研究结果表明，对多维数据的综合分析有可能揭示肿瘤发生和发展的机制。
Glioblastoma arises from complex interactions between a variety of genetic alterations and environmental perturbations. Little attention has been paid to understanding how genetic variations, altered gene expression and microRNA (miRNA) expression are integrated into networks which act together to alter regulation and finally lead to the emergence of complex phenotypes and glioblastoma. We identified association of somatic mutations in 14 genes with glioblastoma, of which 8 genes are newly identified, and association of loss of heterozygosity (LOH) is identified in 11 genes with glioblastoma, of which 9 genes are newly discovered. By gene coexpression network analysis, we indentified 15 genes essential to the function of the network, most of which are cancer related genes. We also constructed miRNA coexpression networks and found 19 important miRNAs of which 3 were significantly related to glioblastoma patients' survival. We identified 3,953 predicted miRNA-mRNA pairs, of which 14 were previously verified by experiments in other groups. Using pathway enrichment analysis we also found that the genes in the target network of the top 19 important miRNAs were mainly involved in cancer related signaling pathways, synaptic transmission and nervous systems processes. Finally, we developed new methods to decipher the pathway connecting mutations, expression information and glioblastoma. We indentified 4 cis-expression quantitative trait locus (eQTL): TP53, EGFR, NF1 and PIK3C2G; 262 trans eQTL and 26 trans miRNA eQTL for somatic mutation; 2 cis-eQTL: NRAP and EGFR; 409 trans- eQTL and 27 trans- miRNA eQTL for lost of heterozygosity (LOH) mutation. Our results demonstrate that integrated analysis of multi-dimensional data has the potential to unravel the mechanism of tumor initiation and progression.
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影响因子：
7
作者：
Gennarino, Vincenzo Alessandro;Sardiello, Marco;Banfi, Sandro
通讯作者：
Banfi, Sandro
影响因子：
3.5
作者：
Dartnell, L;Simeonidis, E;Papageorgiou, LG
通讯作者：
Papageorgiou, LG
影响因子：
9.8
作者：
Brooks, AS;Bertoli-Avella, AM;Hofstra, RMW
通讯作者：
Hofstra, RMW
miR2Disease：人类疾病中 microRNA 失调的手动数据库
影响因子：
14.9
作者：
Jiang Q;Wang Y;Hao Y;Juan L;Teng M;Zhang X;Li M;Wang G;Liu Y
通讯作者：
Liu Y
DOI：
10.1006/bbrc.2000.3449
发表时间：
2000-09-16
影响因子：
3.1
作者：
Imoto, I;Pimkhaokham, A;Inazawa, J
通讯作者：
Inazawa, J