Recurrent tumor-specific regulation of alternative polyadenylation of cancer-related genes.
Recurrent tumor-specific regulation of alternative polyadenylation of cancer-related genes.
复制标题
DOI：
10.1186/s12864-018-4903-7
复制
发表时间：
2018-07-13
期刊：
影响因子：
4.4
通讯作者：
Birol I
中科院分区：
文献类型：
--
作者：
Xue Z;Warren RL;Gibb EA;MacMillan D;Wong J;Chiu R;Hammond SA;Yang C;Nip KM;Ennis CA;Hahn A;Reynolds S;Birol I
选择性多聚腺苷酸化（阿帕）导致信使RNA分子具有不同的3 '非翻译区（3' UTR），从而影响分子的稳定性、定位和翻译。阿帕是普遍存在的，与癌症有关。早期关于阿帕的报道集中在3' UTR长度修饰，并且通常将阿帕事件表征为3' UTR缩短或延长。然而，这样的表征过度简化了转录本3′端的处理，并未能充分描述我们观察到的各种情况。我们建立了一个基于云的靶向从头转录组装和分析管道，其中包含我们以前开发的切割位点预测工具KLEAT。我们应用这个管道来阐明癌症基因组图谱（TCGA）中9939个肿瘤和729个正常组织样本中114个基因的阿帕谱。来自33种癌症类型的10，668个RNA-Seq样本的完整集合尚未被先前的阿帕研究使用。通过比较正常和肿瘤样本组之间预测切割位点的频率，我们在13种癌症类型中确定了77个肿瘤特异性阿帕调控事件（即基因-癌症类型对）;对于15个基因，这种调控在多种癌症中反复出现。我们的结果也支持了先前的报告，该报告显示了多种癌症中FGF 2的3' UTR缩短。然而，我们鉴定的超过一半的事件显示3' UTR长度的复杂变化，其抵抗简单的分类，如缩短或延长。阿帕的复发性肿瘤特异性调节在癌症中广泛存在。然而，我们在TCGA RNA-seq数据中观察到的调控模式不能被描述为简单的3' UTR缩短或延长。对这一复杂、微妙的监管格局的持续研究将进一步深入了解其在肿瘤形成和发展中的作用。本文的在线版本（10.1186/s12864-018-4903-7）包含补充材料，可供授权用户使用。
Alternative polyadenylation (APA) results in messenger RNA molecules with different 3′ untranslated regions (3’ UTRs), affecting the molecules’ stability, localization, and translation. APA is pervasive and implicated in cancer. Earlier reports on APA focused on 3’ UTR length modifications and commonly characterized APA events as 3’ UTR shortening or lengthening. However, such characterization oversimplifies the processing of 3′ ends of transcripts and fails to adequately describe the various scenarios we observe. We built a cloud-based targeted de novo transcript assembly and analysis pipeline that incorporates our previously developed cleavage site prediction tool, KLEAT. We applied this pipeline to elucidate the APA profiles of 114 genes in 9939 tumor and 729 tissue normal samples from The Cancer Genome Atlas (TCGA). The full set of 10,668 RNA-Seq samples from 33 cancer types has not been utilized by previous APA studies. By comparing the frequencies of predicted cleavage sites between normal and tumor sample groups, we identified 77 events (i.e. gene-cancer type pairs) of tumor-specific APA regulation in 13 cancer types; for 15 genes, such regulation is recurrent across multiple cancers. Our results also support a previous report showing the 3’ UTR shortening of FGF2 in multiple cancers. However, over half of the events we identified display complex changes to 3’ UTR length that resist simple classification like shortening or lengthening. Recurrent tumor-specific regulation of APA is widespread in cancer. However, the regulation pattern that we observed in TCGA RNA-seq data cannot be described as straightforward 3’ UTR shortening or lengthening. Continued investigation into this complex, nuanced regulatory landscape will provide further insight into its role in tumor formation and development. The online version of this article (10.1186/s12864-018-4903-7) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
64.5
作者：
Hogg JR;Goff SP
通讯作者：
Goff SP
影响因子：
4.5
作者：
Hoffman Y;Bublik DR;Ugalde AP;Elkon R;Biniashvili T;Agami R;Oren M;Pilpel Y
通讯作者：
Pilpel Y
影响因子：
10.5
作者：
Lianoglou S;Garg V;Yang JL;Leslie CS;Mayr C
通讯作者：
Mayr C
DOI：
10.1093/bioinformatics/btu558
发表时间：
2014-12-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Chu J;Sadeghi S;Raymond A;Jackman SD;Nip KM;Mar R;Mohamadi H;Butterfield YS;Robertson AG;Birol I
通讯作者：
Birol I
影响因子：
5.8
作者：
Goodstadt, Leo
通讯作者：
Goodstadt, Leo