A network of epigenetic modifiers and DNA repair genes controls tissue-specific copy number alteration preference
A network of epigenetic modifiers and DNA repair genes controls tissue-specific copy number alteration preference
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DOI：
10.7554/elife.16519
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发表时间：
2016-11-10
期刊：
影响因子：
7.7
通讯作者：
Schaefer, Martin H.
中科院分区：
文献类型：
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作者：
Cramer, Dina;Serrano, Luis;Schaefer, Martin H.
癌症患者的拷贝数改变（CNA）在其数量、长度和位置上显示出很大的变异性，但这种变异性的来源尚不清楚。CNA的数量和长度与患者的生存率相关，提示临床相关性。我们已经确定了在具有很少或很多CNA的样品中倾向于突变的基因，我们称之为CONIM基因（COpy Number Instability Modulators）。CONIM蛋白聚集成一个紧密连接的物理相互作用的子网络，其中许多是表观遗传修饰剂。因此，我们研究了起源组织的表观基因组如何影响CNA断点的位置和所得CNA的性质。我们发现，异染色质的存在下，在组织的起源有助于复发和长度的CNA在各自的癌症类型。
Copy number alterations (CNAs) in cancer patients show a large variability in their number, length and position, but the sources of this variability are not known. CNA number and length are linked to patient survival, suggesting clinical relevance. We have identified genes that tend to be mutated in samples that have few or many CNAs, which we term CONIM genes (COpy Number Instability Modulators). CONIM proteins cluster into a densely connected subnetwork of physical interactions and many of them are epigenetic modifiers. Therefore, we investigated how the epigenome of the tissue-of-origin influences the position of CNA breakpoints and the properties of the resulting CNAs. We found that the presence of heterochromatin in the tissue-of origin contributes to the recurrence and length of CNAs in the respective cancer type.