Pan-Cancer Analysis Reveals the Diverse Landscape of Novel Sense and Antisense Fusion Transcripts

Neetha Nanoth Vellichirammal, Abrar Albahrani, Jasjit K. Banwait, Nitish K. Mishra, You Li, Shrabasti Roychoudhury, Mathew J. Kling, Sameer Mirza, Kishor K. Bhakat, Vimla Band, Shantaram S. Joshi, Chittibabu Guda

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1379-1398
Number of pages20
JournalMolecular Therapy - Nucleic Acids
Volume19
DOIs
StatePublished - Mar 6 2020

    Fingerprint

Keywords

  • CCLE
  • ChimeRScope
  • TCGA
  • antisense fusion
  • cancer
  • fusion transcripts
  • pan-cancer analysis
  • primary tumor-cell line comparison
  • recurrent fusions
  • therapeutic targets

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Vellichirammal, N. N., Albahrani, A., Banwait, J. K., Mishra, N. K., Li, Y., Roychoudhury, S., Kling, M. J., Mirza, S., Bhakat, K. K., Band, V., Joshi, S. S., & Guda, C. (2020). Pan-Cancer Analysis Reveals the Diverse Landscape of Novel Sense and Antisense Fusion Transcripts. Molecular Therapy - Nucleic Acids, 19, 1379-1398. https://doi.org/10.1016/j.omtn.2020.01.023