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SFyNCS detects oncogenic fusions involving non-coding sequences in cancer

Xiaoming Zhong, Jingyun Luan, Anqi Yu, Anna Lee-Hassett, Yuxuan Miao, Lixing Yang
doi: https://doi.org/10.1101/2023.04.03.535462
Xiaoming Zhong
1Ben May Department for Cancer Research, University of Chicago, Chicago IL, USA
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Jingyun Luan
1Ben May Department for Cancer Research, University of Chicago, Chicago IL, USA
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Anqi Yu
1Ben May Department for Cancer Research, University of Chicago, Chicago IL, USA
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Anna Lee-Hassett
1Ben May Department for Cancer Research, University of Chicago, Chicago IL, USA
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Yuxuan Miao
1Ben May Department for Cancer Research, University of Chicago, Chicago IL, USA
2University of Chicago Comprehensive Cancer Center, Chicago, IL, USA
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  • For correspondence: lixingyang@uchicago.edu miaoy@uchicago.edu
Lixing Yang
1Ben May Department for Cancer Research, University of Chicago, Chicago IL, USA
2University of Chicago Comprehensive Cancer Center, Chicago, IL, USA
3Department of Human Genetics, University of Chicago, Chicago IL, USA
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  • For correspondence: lixingyang@uchicago.edu miaoy@uchicago.edu
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Abstract

Fusion genes are well-known cancer drivers. However, very few known oncogenic fusions involve non-coding sequences. We develop SFyNCS with superior performance to detect fusions of both protein-coding genes and non-coding sequences from transcriptomic sequencing data. We validate fusions using somatic structural variations detected from the genomes. This allows us to comprehensively evaluate various fusion detection and filtering strategies and parameters. We detect 165,139 fusions in 9,565 tumor samples across 33 tumor types in the Cancer Genome Atlas cohort. Among them, 72% of the fusions involve non-coding sequences and many are recurrent. We discover two long non-coding RNAs recurrently fused with various partner genes in 32% of dedifferentiated liposarcomas and experimentally validated the oncogenic functions in mouse model.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted April 06, 2023.
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SFyNCS detects oncogenic fusions involving non-coding sequences in cancer
Xiaoming Zhong, Jingyun Luan, Anqi Yu, Anna Lee-Hassett, Yuxuan Miao, Lixing Yang
bioRxiv 2023.04.03.535462; doi: https://doi.org/10.1101/2023.04.03.535462
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SFyNCS detects oncogenic fusions involving non-coding sequences in cancer
Xiaoming Zhong, Jingyun Luan, Anqi Yu, Anna Lee-Hassett, Yuxuan Miao, Lixing Yang
bioRxiv 2023.04.03.535462; doi: https://doi.org/10.1101/2023.04.03.535462

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