Gene fusions – genomic events where parts of two separate genes are connected to form a single hybrid gene – have been found in almost every type of human cancer. With over 10,000 different fusions identified to date (1), it’s unsurprising that they play a role in so many different forms of the disease. In particular, gene fusions involving kinases, such as ALK, RET, ROS1, FGFR, and NTRK, are known to be involved in multiple cancers. The discoveries of those fusions meant new opportunities for patients to receive therapy in clinical trials – but before those treatments could be offered, laboratories needed a clinical-grade test that could detect multiple types of gene fusions, including novel ones. And that’s why Sameek Roychowdhury’s group at the Ohio State Cancer Center developed OSU-SpARKFuse (2) – a new type of gene fusion assay.
“OSU-SpARKFuse involves focused sequencing of tumor RNA through hybridization-based enrichment of a selected panel of transcripts,” explains Roychowdhury. “Because it is not an amplicon-based approach, the assay is not limited to select exons and directionality of gene fusions, and has the capacity to discover fusions involving new gene partners, breakpoints, and orientations.” Why is the test so valuable? Gene fusions can happen in any type of cancer (though they’re more common in certain types, such as thyroid, lung, and cholangiocarcinoma) – which means that the test could hold value for any patient diagnosed with the disease. Currently, a clinical trial at James Cancer Hospital at the Ohio State University offers OSU-SpARKFuse to patients with metastatic or advanced stage cancer of any type. Such RNA sequencing has value even beyond gene fusions, though. The assay can also detect other transcriptome events, such as splicing or exon skipping. Roychowdhury emphasizes the power of clinical-grade RNA sequencing to detect splicing and gene expression, and to enable immune cell profiling, giving just one example from his own experience: “A young woman with metastatic lung cancer was found to have MET exon skipping and benefited from a MET inhibitor in a clinical trial.”
Newsletters
Receive the latest pathology news, personalities, education, and career development – weekly to your inbox.
References
- National Cancer Institute, “Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer” (2017). Available at: http://bit.ly/2h7mtKa. Accessed September 15, 2017. JW Reeser et al., “Validation of a targeted RNA sequencing assay for kinase fusion detection in solid tumors”, J Mol Diagn, 19, 682–696 (2017). PMID: 28802831.
