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Abstract Background: Gene fusions, resulting from chromosomal rearrangements, play a critical role in the oncogenesis of various cancers, often acting as diagnostic markers and therapeutic targets. Their detection is important for understanding tumor biology and guiding personalized treatment strategies. With the evolution of economical sequencing technologies, hypothesis-free gene fusion detection in cancer genomics is becoming more accessible. This study demonstrates the use of the cost-effective Ultima Genomics UG100 platform for a comprehensive analysis of gene fusions, uniquely integrating Whole Genome Sequencing (WGS) and Whole Transcriptome Sequencing (WTS). This integration capitalizes on the strengths of both methods: WGS, which enables a broad analysis of structural variations including extragenic events, and WTS for more functional characterization of expressed gene fusions and abnormal isoforms, offering a synergistic approach that enhances the detection and characterization of genomic rearrangements. Methods: Five cancer cell lines (K562, THP-1, NCI-H660, Kasumi-1, MV4-11) with 29 previously detected gene fusions were sequenced, using both WTS and WGS, in addition to a standard fusion reference sample (Seraseq Fusion RNA Mix, with 16 RNA fusions). The libraries were sequenced on a UG100 sequencer using single ended reads of length ~250bp and analyzed with publicly available software: STAR-Fusion, combined with FusionInspector were used to detect RNA fusions; Manta and GridSS were used to detect DNA structural variations, including translocations. Results: 93% of the documented fusion events were detected in DNA and in RNA, in addition to the 16 evaluated just in RNA (100% detected). Sequence data from both WTS and WGS on the UG100 platform successfully identified a spectrum of gene fusions in both DNA and RNA, thereby confirming the platform's detection capabilities in both types of assays. The structural variation events detected in the WGS were comprised mainly of translocations, but also deletions and duplications. Conclusions: The Ultima Genomics UG100 sequencer has proven to be a cost-effective and efficient tool for the genome-wide discovery and validation of gene fusions, which can be impactful in clinical oncology settings. This study underscores the potential of using an integrated WTS and WGS approach on a single platform to advance our understanding of the genomic complexity of cancer, paving the way for more effective diagnostic and therapeutic strategies. Citation Format: Gila Lithwick-Yanai, Sarah Pollock, Danit Lebanony, Keren Ben Simhon, Sima Benjamin, David Bogumil, Nika Iremadze, Matt Sexton, Peleg Winer, Maya Levy, Shlomit Gilad, Josh Haimes, Giulia Corbet, Jennifer Pavlica, Doron Lipson. Cost-effective, comprehensive detection of gene fusions from DNA and RNA using the UG100 sequencer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 315.
Lithwick‐Yanai et al. (Fri,) studied this question.