Pan-Cancer Analysis Reveals the Diverse Landscape of Novel Sense and Antisense Fusion Transcripts
Pan-Cancer Analysis Reveals the Diverse Landscape of Novel Sense and Antisense Fusion Transcripts
复制标题
DOI：
10.1016/j.omtn.2020.01.023
复制
发表时间：
2020-01
期刊：
影响因子：
--
通讯作者：
N. N. Vellichirammal-N.;Abrar Albahrani;Jasjit K. Banwait;N. Mishra;You Li;Shrabasti Roychoudhury;Mathew J. Kling;S. Mirza;K. Bhakat;V. Band;S. Joshi;C. Guda
中科院分区：
文献类型：
--
作者：
N. N. Vellichirammal-N.;Abrar Albahrani;Jasjit K. Banwait;N. Mishra;You Li;Shrabasti Roychoudhury;Mathew J. Kling;S. Mirza;K. Bhakat;V. Band;S. Joshi;C. Guda
有助于致癌性的基因融合可以被探索用于鉴定癌症生物标志物和潜在的药物靶点。为了研究癌症中融合转录物的性质和分布，我们使用一种新型融合检测算法ChimeRScope检查了TCGA（癌症基因组图谱）中33种不同癌症的约9，000种原发性肿瘤的转录组数据沿着CCLE（癌症细胞系百科全书）的细胞系数据。我们确定了几个融合与正义（规范，39%）或反义（非规范，61%）转录复发的癌症。在我们的研究中发现的大多数复发性非典型融合是新的，未探索的，并且在癌症中表现出高度可变的特征，乳腺癌和胶质母细胞瘤分别具有最高和最低的比率。总的来说，在这项研究中，从TCGA中确定了4，344例复发性融合，其中70%是新的。对20种癌症的802种肿瘤衍生细胞系转录组数据的额外分析揭示了原发性肿瘤和相应细胞系之间复发性融合谱的显著差异。通过检查全基因组测序（WGS）数据中的结构变异证据或通过融合接头的桑格测序来验证规范和非规范融合的子集。在我们的研究中发现的几个复发性融合基因显示出在篮子试验中药物再利用的前景，并为机制研究提供了机会。
Gene fusions that contribute to oncogenicity can be explored for identifying cancer biomarkers and potential drug targets. To investigate the nature and distribution of fusion transcripts in cancer, we examined the transcriptome data of about 9,000 primary tumors from 33 different cancers in TCGA (The Cancer Genome Atlas) along with cell line data from CCLE (Cancer Cell Line Encyclopedia) using ChimeRScope, a novel fusion detection algorithm. We identified several fusions with sense (canonical, 39%) or antisense (non-canonical, 61%) transcripts recurrent across cancers. The majority of the recurrent non-canonical fusions found in our study are novel, unexplored, and exhibited highly variable profiles across cancers, with breast cancer and glioblastoma having the highest and lowest rates, respectively. Overall, 4,344 recurrent fusions were identified from TCGA in this study, of which 70% were novel. Additional analysis of 802 tumor-derived cell line transcriptome data across 20 cancers revealed significant variability in recurrent fusion profiles between primary tumors and corresponding cell lines. A subset of canonical and non-canonical fusions was validated by examining the structural variation evidence in whole-genome sequencing (WGS) data or by Sanger sequencing of fusion junctions. Several recurrent fusion genes identified in our study show promise for drug repurposing in basket trials and present opportunities for mechanistic studies.