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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 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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Digital Access to Scholarship at Harvard  

Autor(es)

Shankar, Ganesh Mani -  Francis, Joshua M. -  Rinne, Mikael Lee -  Ramkissoon, Shakti -  Huang, Franklin W -  Venteicher, Andrew S -  Akama -  Garren, Elliot H. -  Kang, Yun Jee -  Lelic, Nina -  Kim, James C. -  Brown, Loreal E. -  Charbonneau, Sarah K -  Golby, Alexandra Jacqueline -  Sekhar Pedamallu, Chandra -  Hoang, Mai P -  Sullivan, Ryan Joseph -  Cherniack, Andrew D. -  Garraway, Levi Alexander -  Stemmer -  Rachamimov, Anat -  Reardon, David Allen -  Wen, Patrick Yung Chih -  Brastianos, Priscilla Kalliope -  Curry, William Thomas -  Barker, Frederick George -  Hahn, William Chun -  Nahed, Brian Vala -  Ligon, Keith Lloyd -  Louis, David N. -  Cahill, Daniel P. -  Meyerson, Matthew Langer - 

Id.: 70196032

Idioma: inglés (Estados Unidos)  - 

Versión: 1.0

Estado: Final

Tipo de recurso: Journal Article  - 

Tipo de Interactividad: Expositivo

Nivel de Interactividad: muy bajo

Audiencia: Estudiante  -  Profesor  -  Autor  - 

Estructura: Atomic

Coste: no

Copyright: sí

: open

Requerimientos técnicos:  Browser: Any - 

Relación: [References] doi:10.1001/jamaoncol.2015.0917
[References] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872045/
[References] JAMA Oncology

Fecha de contribución: 10-nov-2017

Contacto:

Localización:
* Shankar, Ganesh M., Joshua M. Francis, Mikael L. Rinne, Shakti H. Ramkissoon, Franklin W. Huang, Andrew S. Venteicher, Elliot H. Akama-Garren, et al. 2015. “Rapid Intraoperative Molecular Characterization of Glioma.” JAMA Oncology 1 (5) (August 1): 662. doi:10.1001/jamaoncol.2015.0917.
* 2374-2437

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