Comprehensive analysis of long non-coding RNAs in ovarian cancer reveals global patterns and targeted DNA amplification.
Comprehensive analysis of long non-coding RNAs in ovarian cancer reveals global patterns and targeted DNA amplification.
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DOI：
10.1371/journal.pone.0080306
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Larsson E
中科院分区：
文献类型：
--
作者：
Akrami R;Jacobsen A;Hoell J;Schultz N;Sander C;Larsson E
长链非编码RNA（lncRNA）正在成为细胞生理学的有效调节因子，最近的研究强调了它们在肿瘤发展中的作用。然而，虽然已建立的蛋白质编码癌基因和肿瘤抑制因子通常显示肿瘤中灶性DNA拷贝数改变的惊人模式，但lncRNA在很大程度上缺乏类似的证据。在此，我们报告了基于癌症基因组图谱（TCGA）分子图谱的高级别浆液性卵巢腺癌中GENCODE lncRNA的基因组分析。使用基因组拷贝数数据和深度覆盖转录组测序，我们获得了407个原发性肿瘤中10，419个lncRNA的双重拷贝数和表达数据。我们描述了lncRNA拷贝数和表达之间的全球相关性，并将建立的表达亚型与不同的lncRNA签名相关联。通过检查缺乏蛋白质编码靶点的局灶性拷贝数变化区域，我们鉴定了1号染色体上的基因间lncRNA OVAL，其在肿瘤子集中显示出狭窄的局灶性基因组扩增。虽然在大多数肿瘤中弱表达，但局灶性扩增与强OVAL转录激活一致。其他16种癌症类型的筛查显示浆液性子宫内膜癌的模式相似。这表明，基因间lncRNA可以通过体细胞拷贝数扩增特异性靶向，提示在肿瘤起始或进展中的功能参与。我们的分析提供了可检验的假设，并为基于TCGA和其他大规模癌症基因组学数据集的lncRNA的进一步研究铺平了道路。
Long non-coding RNAs (lncRNAs) are emerging as potent regulators of cell physiology, and recent studies highlight their role in tumor development. However, while established protein-coding oncogenes and tumor suppressors often display striking patterns of focal DNA copy-number alteration in tumors, similar evidence is largely lacking for lncRNAs. Here, we report on a genomic analysis of GENCODE lncRNAs in high-grade serous ovarian adenocarcinoma, based on The Cancer Genome Atlas (TCGA) molecular profiles. Using genomic copy-number data and deep coverage transcriptome sequencing, we derived dual copy-number and expression data for 10,419 lncRNAs across 407 primary tumors. We describe global correlations between lncRNA copy-number and expression, and associate established expression subtypes with distinct lncRNA signatures. By examining regions of focal copy-number change that lack protein-coding targets, we identified an intergenic lncRNA on chromosome 1, OVAL, that shows narrow focal genomic amplification in a subset of tumors. While weakly expressed in most tumors, focal amplification coincided with strong OVAL transcriptional activation. Screening of 16 other cancer types revealed similar patterns in serous endometrial carcinomas. This shows that intergenic lncRNAs can be specifically targeted by somatic copy-number amplification, suggestive of functional involvement in tumor initiation or progression. Our analysis provides testable hypotheses and paves the way for further study of lncRNAs based on TCGA and other large-scale cancer genomics datasets.
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影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
影响因子：
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通讯作者：
--
影响因子：
64.8
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通讯作者：
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影响因子：
64.8
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通讯作者：
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影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ