Importance: Conclusive intraoperative pathologic confirmation of diffuse infiltrative glioma guides the decision to pursue definitive neurosurgical resection. Establishing the intraoperative diagnosis by histologic analysis can be difficult in low-cellularity infiltrative gliomas. Therefore, we developed a rapid and sensitive genotyping assay to detect somatic single-nucleotide variants in the telomerase reverse transcriptase (TERT) promoter and isocitrate dehydrogenase 1 (IDH1). Observations: This assay was applied to tissue samples from 190 patients with diffuse gliomas, including archived fixed and frozen specimens and tissue obtained intraoperatively. Results demonstrated 96%sensitivity (95%CI, 90%-99%) and 100% specificity (95%CI, 95%-100%) for World Health Organization grades II and III gliomas. In a series of live cases, glioma-defining mutations could be identified within 60 minutes, which could facilitate the diagnosis in an intraoperative timeframe. Conclusions and Relevance: The genotypingmethod described herein can establish the diagnosis of low-cellularity tumors like glioma and could be adapted to the point-of-care diagnosis of other lesions that are similarly defined by highly recurrent somatic mutations.
Bibliographical noteFunding Information:
Dr Shankar is supported by grant R25NS065743 from the National Institutes of Health (NIH) National Institutes of Neurologic Disorders and Stroke, the American Brain Tumor Association Basic Research Fellowship supported by the Humor to Fight the Tumor Event Committee. Dr Rinne is supported by a National Cancer Institute (NCI) K12 Training Fellowship and the Claudia Adams Barr Program in Basic Cancer Research. Dr Cahill is supported by the BurroughsWellcome Career Award and the NIH-NCI Specialized Programs of Research Excellence (SPORE) grant P50CA165962.
Funding/Support: Dr Shankar is supported by
consultant for N-of-One Inc. Drs Cherniack and Meyerson have received a commercial research grant from Bayer. Dr Garraway received a commercial research grant from Novartis and is a consultant and advisory board member for Novartis, Foundation Medicine, and Boehringer Ingelheim; he also has equity interest in Foundation Medicine. Dr Reardon is an advisory board member for Abbvie, Cavion, Genentech/Roche, Merck, Midatech, Novartis, Stemline Therapeutics, Amgen and Momenta Pharmaceuticals, and is a speaker for Roche/Genentech and Merck. Dr Wen is an advisory board member for AbbVie, Cavion, Celldex, Cubist, Genentech/Roche, Midatech, Momenta, Novartis, Novocure, SigmaTau, and Vascular Biogenics and is a speaker for Merck. Dr Meyerson has ownership interest in and is a consultant and advisory board member for Foundation Medicine. A provisional patent application for this technology has been filed. No other disclosures are reported.
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