Pan-Cancer Analysis Reveals the Diverse Landscape of Novel Sense and Antisense Fusion Transcripts
| Autor: | Shantaram S. Joshi, Jasjit K. Banwait, Kishor K. Bhakat, Chittibabu Guda, Neetha Nanoth Vellichirammal, Mathew J. Kling, Shrabasti Roychoudhury, Sameer Mirza, Abrar Albahrani, Vimla Band, Nitish K. Mishra, You Li |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
pan-cancer analysis Computational biology Biology primary tumor-cell line comparison therapeutic targets Article ChimeRScope Transcriptome Structural variation Fusion gene 03 medical and health sciences symbols.namesake 0302 clinical medicine Breast cancer CCLE Drug Discovery Sense (molecular biology) medicine cancer Gene Sanger sequencing lcsh:RM1-950 antisense fusion recurrent fusions TCGA medicine.disease fusion transcripts 3. Good health lcsh:Therapeutics. Pharmacology 030104 developmental biology 030220 oncology & carcinogenesis symbols Molecular Medicine Cancer biomarkers |
| Zdroj: | Molecular Therapy. Nucleic Acids Molecular Therapy: Nucleic Acids, Vol 19, Iss, Pp 1379-1398 (2020) |
| ISSN: | 2162-2531 |
| Popis: | 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. Keywords: pan-cancer analysis, antisense fusion, TCGA, CCLE, fusion transcripts, primary tumor-cell line comparison, cancer, ChimeRScope, therapeutic targets, recurrent fusions |
| Databáze: | OpenAIRE |
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