Genome-wide network analysis of Wnt signaling in three pediatric cancers.
Genome-wide network analysis of Wnt signaling in three pediatric cancers.
复制标题
三种儿科癌症 Wnt 信号传导的全基因组网络分析。
DOI：
10.1038/srep02969
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发表时间：
2013
影响因子：
4.6
通讯作者：
Zheng,JieJ
中科院分区：
文献类型：
--
作者：
Bao,Ju;Lee,Ho-Jin;Zheng,JieJ
基因组结构改变在儿科癌症中很常见，儿科癌症基因组计划生成的数据分析显示，许多Wnt信号相关基因中存在此类肿瘤相关改变。大多数儿童癌症被认为发生在发育中的组织中，这些组织在早期器官形成、生长和成熟过程中经历了大量扩张，Wnt信号在这一发展中起着重要作用。我们研究了三种小儿肿瘤——髓母细胞瘤、早期t细胞前体急性淋巴细胞白血病和视网膜母细胞瘤——它们在Wnt信号通路中显示出多种基因组结构变异。我们对这一通路进行了数学建模，以研究癌症相关结构变异对Wnt信号传导的影响。令人惊讶的是，我们发现，即使在不同的癌症、不同的突变和不同的Wnt相关基因的背景下，标准Wnt信号的结果测量在匹配的癌细胞和正常细胞中始终相似。我们的研究结果表明，癌细胞通过发生多种突变来维持正常水平的Wnt信号。
Genomic structural alteration is common in pediatric cancers and analysis of data generated by the Pediatric Cancer Genome Project reveals such tumor-related alterations in many Wnt signaling–associated genes. Most pediatric cancers are thought to arise within developing tissues that undergo substantial expansion during early organ formation, growth and maturation and Wnt signaling plays an important role in this development. We examined three pediatric tumors—medullobastoma, early T-cell precursor acute lymphoblastic leukemia and retinoblastoma—that show multiple genomic structural variations within Wnt signaling pathways. We mathematically modeled this pathway to investigate the effects of cancer-related structural variations on Wnt signaling. Surprisingly, we found that an outcome measure of canonical Wnt signaling was consistently similar in matched cancer cells and normal cells, even in the context of different cancers, different mutations and different Wnt-related genes. Our results suggest that the cancer cells maintain a normal level of Wnt signaling by developing multiple mutations.