Volders Pieter-Jan, Lefever Steve, Baute Shalina, Nuytens Justine, Vanderheyden Katrien, Menten Björn, Mestdagh Pieter, Vandesompele Jo
Center for Medical Genetics (CMGG), Ghent University, 9000 Ghent, Belgium.
Cancer Research Institute Ghent (CRIG), 9000 Ghent, Belgium.
Noncoding RNA. 2018 Sep 13;4(3):21. doi: 10.3390/ncrna4030021.
The landscape of somatic copy-number alterations (SCNAs) affecting long non-coding RNAs (lncRNAs) in human cancers remains largely unexplored. While the majority of lncRNAs remain to be functionally characterized, several have been implicated in cancer development and metastasis. Considering the plethora of lncRNAs genes that have been currently reported, it is conceivable that many more lncRNAs might function as oncogenes or tumor suppressor genes. We devised a strategy to detect focal lncRNA SCNAs using a custom DNA microarray platform probing 10,519 lncRNA genes. By screening a panel of 80 cancer cell lines, we detected numerous focal aberrations targeting one or multiple lncRNAs without affecting neighboring protein-coding genes. These focal aberrations are highly suggestive for a tumor suppressive or oncogenic role of the targeted lncRNA gene. Although functional validation remains an essential step in the further characterization of the involved candidate cancer lncRNAs, our results provide a direct way of prioritizing candidate lncRNAs that are involved in cancer pathogenesis.
影响人类癌症中长链非编码RNA（lncRNA）的体细胞拷贝数改变（SCNA）情况在很大程度上仍未得到探索。虽然大多数lncRNA的功能仍有待确定，但已有一些lncRNA与癌症的发生发展和转移有关。鉴于目前已报道的lncRNA基因数量众多，可以想象，更多的lncRNA可能作为癌基因或肿瘤抑制基因发挥作用。我们设计了一种策略，使用一个定制的DNA微阵列平台来检测局部lncRNA SCNA，该平台可探测10519个lncRNA基因。通过筛选一组80个癌细胞系，我们检测到许多针对一个或多个lncRNA的局部畸变，而不影响邻近的蛋白质编码基因。这些局部畸变强烈暗示了靶向lncRNA基因的肿瘤抑制或致癌作用。尽管功能验证仍然是进一步表征相关候选癌症lncRNA的关键步骤，但我们的结果提供了一种直接的方法来对参与癌症发病机制的候选lncRNA进行优先级排序。
