Rapid intraoperative molecular characterization of glioma

Ganesh M. Shankar, Joshua M. Francis, Mikael L. Rinne, Shakti H. Ramkissoon, Franklin W. Huang, Andrew S. Venteicher, Elliot H. Akama-Garren, Yun Jee Kang, Nina Lelic, James C. Kim, Loreal E. Brown, Sarah K. Charbonneau, Alexandra J. Golby, Chandra Sekhar Pedamallu, Mai P. Hoang, Ryan J. Sullivan, Andrew D. Cherniack, Levi A. Garraway, Anat Stemmer-Rachamimov, David A. ReardonPatrick Y. Wen, Priscilla K. Brastianos, William T. Curry, Fred G. Barker, William C. Hahn, Brian V. Nahed, Keith L. Ligon, David N. Louis, Daniel P. Cahill, Matthew Meyerson

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)662-667
Number of pages6
JournalJAMA Oncology
Volume1
Issue number5
DOIs
StatePublished - Aug 2015

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    Shankar, G. M., Francis, J. M., Rinne, M. L., Ramkissoon, S. H., Huang, F. W., Venteicher, A. S., Akama-Garren, E. H., Kang, Y. J., Lelic, N., Kim, J. C., Brown, L. E., Charbonneau, S. K., Golby, A. J., Pedamallu, C. S., Hoang, M. P., Sullivan, R. J., Cherniack, A. D., Garraway, L. A., Stemmer-Rachamimov, A., ... Meyerson, M. (2015). Rapid intraoperative molecular characterization of glioma. JAMA Oncology, 1(5), 662-667. https://doi.org/10.1001/jamaoncol.2015.0917