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Rapid Intraoperative Molecular Characterization of Glioma.

Shankar GM, Francis JM, Rinne ML, Ramkissoon SH, Huang FW, Venteicher AS, Akama-Garren EH, Kang YJ, Lelic N, Kim JC, Brown LE, Charbonneau SK, Golby AJ, Sekhar Pedamallu C, Hoang MP, Sullivan RJ, Cherniack AD, Garraway LA, Stemmer-Rachamimov A9, Reardon DA, Wen PY, Brastianos PK, Curry WT8, Barker FG 2nd, Hahn WC, Nahed BV, Ligon KL, Louis DN, Cahill DP, Meyerson M.

JAMA Oncol. 2015 Aug;1(5):662-7. doi: 10.1001/jamaoncol.2015.0917.




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).



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.



The genotyping method 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.

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