Columbus, Ohio – An assay that identifies a peculiar but important abnormality in cancer cells has been developed and validated by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).
The assay, called OSU-SpARKFuse (Ohio State University-Spanning Actionable RNA Kinase Fusions), detects a genetic change called gene fusions in solid tumors. The assay and its validation are published in The Journal of Molecular Diagnostics.
Gene fusions happen when parts of two different genes join together. Gene fusions can happen, for example, when a piece of one chromosome becomes attached to another. Such chromosome "translocations" can join two genes that together become a major driver of cancer-cell and tumor growth.
Targeted therapies are becoming increasingly available that block the activity of fusion genes, particular those involving kinase genes. Whereas current assays for detecting gene fusions require previous knowledge of both genes involved in the fusion, OSU-SpARKFuse was designed to accurately detect fusions when only one of the genes is known, which allows for the discovery of novel gene fusions.
"We designed OSU-SpARKFuse to meet these needs and to identify patients who are eligible for novel therapies such as FGFR inhibitors or NTRK inhibitors that target gene fusions," says principal investigator Sameek Roychowdhury, MD, PhD, assistant professor in the Division of Medical Oncology at Ohio State.
"Along with detecting gene fusions, OSU-SpARKFuse can provide gene-expression analysis, detect single-nucleotide changes and identify alternative splicing events and resistance genes," says first author Julie Reeser, PhD, technical supervisor of the OSUCCC – James Cancer Genomics Laboratory.
"Additionally, OSU-SpARKFuse does not require information regarding the location of the fusion in each gene. It is an accurate, reproducible, cost-effective assay that detects gene fusions across many genes and from the small samples of tumor tissue obtained by biopsy," Reeser adds.
Roychowdhury, Reeser and their colleagues validated the performance of OSU-SpARKFuse using 74 positive and 36 negative control specimens. They included 51 cell line samples, 43 formalin-fixed paraffin-embedded tissues and 16 fresh-frozen tissues. (The assay targets 93 kinase and transcription-factor genes.)
Next, they used the assay to assess gene-fusion status in 95 tissue samples from patients with advanced cancer as part of an Ohio State clinical tumor sequencing study (OSU-13053, NCT02090530) designed and led by Roychowdhury.
Evaluation of the patient samples revealed a novel fusion of the RET gene (RET- OLFM4) in a patient with small-bowel cancer. It also led to the discovery of a KLK2-FGFR2 fusion in a patient with prostate cancer. The patient was then treated with a fibroblast growth factor receptor inhibitor.
"The use of OSU-SpARKFuse in clinical laboratories will help expand the knowledge base of gene fusions in solid tumors, and it could directly affect patient care by detecting therapeutically actionable targets," Roychowdhury says.
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Funding from the American Cancer Society (grant MRSG-12-194-01-TBG), the Prostate Cancer Foundation, National Human Genome Research Institute (grant UM1HG006508-01A1), the National Cancer Institute (grant CA202971), Fore Cancer Research, the American Lung Association, Pelotonia, and a Roessler research scholarship from the Ohio State University College of Medicine supported this research.
Other researchers involved in this study were Julie W. Reeser, Dorrelyn Martin, Jharna Miya, Esko A. Kautto, Ezra Lyon, Eliot Zhu, Michele R. Wing, Amy Smith, Matthew Reeder, Eric Samorodnitsky, Hannah Parks, Karan R. Naik, Nicholas Nowacki, Lianbo Yu, Aharon G. Freud and Joshua Coleman,The Ohio State University; Joseph Gozgit, Marileila Varella-Garcia, Ariad Pharmaceuticals; Kurtis D. Davies, and Dara L. Aisner, University of Colorado.
About the OSUCCC – James
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 49 National Cancer Institute-designated Comprehensive Cancer Centers and one of only a few centers funded by the NCI to conduct both phase I and phase II clinical trials on novel anticancer drugs sponsored by NCI. As the cancer program's 308-bed adult patient-care component, The James is one of the top cancer hospitals in the nation as ranked by U.S. News & World Report and has achieved Magnet® designation, the highest honor an organization can receive for quality patient care and professional nursing practice. At 21 floors with more than 1.1 million square feet, The James is a transformational facility that fosters collaboration and integration of cancer research and clinical cancer care. For more information, please visit cancer.osu.edu.
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Related Journal Article
http://dx.doi.org/10.1016/j.jmoldx.2017.05.006
