Pan-Cancer Analysis Reveals the Diverse Landscape of Novel Sense and Antisense Fusion Transcripts.
CCLE
ChimeRScope
TCGA
antisense fusion
cancer
fusion transcripts
pan-cancer analysis
primary tumor-cell line comparison
recurrent fusions
therapeutic targets
Journal
Molecular therapy. Nucleic acids
ISSN: 2162-2531
Titre abrégé: Mol Ther Nucleic Acids
Pays: United States
ID NLM: 101581621
Informations de publication
Date de publication:
06 Mar 2020
06 Mar 2020
Historique:
received:
18
09
2019
revised:
03
01
2020
accepted:
14
01
2020
entrez:
13
3
2020
pubmed:
13
3
2020
medline:
13
3
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32160708
pii: S2162-2531(20)30058-5
doi: 10.1016/j.omtn.2020.01.023
pmc: PMC7044684
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1379-1398Subventions
Organisme : NCI NIH HHS
ID : F99 CA223064
Pays : United States
Organisme : NIMH NIH HHS
ID : P30 MH062261
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
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