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

Rapid Intraoperative Molecular Characterization of Glioma.

Author information

1
Department of Neurosurgery, Massachusetts General Hospital, Boston2Cancer Program, Broad Institute, Cambridge, Massachusetts.
2
Cancer Program, Broad Institute, Cambridge, Massachusetts3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston Massachusetts.
3
Cancer Program, Broad Institute, Cambridge, Massachusetts4Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston Massachusetts5Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts.
4
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston Massachusetts6Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts7Department of Pathology, Harvard Medical School, Boston, Massachusetts.
5
Department of Neurosurgery, Massachusetts General Hospital, Boston8Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
6
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.
7
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston Massachusetts.
8
Department of Neurosurgery, Massachusetts General Hospital, Boston.
9
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
10
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston Massachusetts10Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts.
11
Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.
12
Cancer Program, Broad Institute, Cambridge, Massachusetts.
13
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston Massachusetts.
14
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston Massachusetts5Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts.
15
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston Massachusetts6Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts7Department of Pathology, Harvard Medical School, Boston, Massachusetts12Center for Molecular On.
16
Cancer Program, Broad Institute, Cambridge, Massachusetts3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston Massachusetts7Department of Pathology, Harvard Medical School, Boston, Massachusetts.

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 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.

PMID:
26181761
PMCID:
PMC4872045
DOI:
10.1001/jamaoncol.2015.0917
[Indexed for MEDLINE]
Free PMC Article

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