title: Rapid Intraoperative Molecular Characterization of Glioma.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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
  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.
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital, Boston2Cancer Program, Broad Institute, Cambridge, Massachusetts.
authors.forename: Ganesh M
authors.initials: GM
authors.lastname: Shankar
authors.affiliation: Cancer Program, Broad Institute, Cambridge, Massachusetts3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston Massachusetts.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Francis
authors.affiliation: Cancer Program, Broad Institute, Cambridge, Massachusetts4Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston Massachusetts5Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Mikael L
authors.initials: ML
authors.lastname: Rinne
authors.affiliation: 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.
authors.forename: Shakti H
authors.initials: SH
authors.lastname: Ramkissoon
authors.affiliation: Cancer Program, Broad Institute, Cambridge, Massachusetts3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston Massachusetts.
authors.forename: Franklin W
authors.initials: FW
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital, Boston8Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Venteicher
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Elliot H
authors.initials: EH
authors.lastname: Akama-Garren
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston Massachusetts.
authors.forename: Yun Jee
authors.initials: YJ
authors.lastname: Kang
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital, Boston.
authors.forename: Nina
authors.initials: N
authors.lastname: Lelic
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: James C
authors.initials: JC
authors.lastname: Kim
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston Massachusetts.
authors.forename: Loreal E
authors.initials: LE
authors.lastname: Brown
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston Massachusetts.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Charbonneau
authors.affiliation: Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston Massachusetts10Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Golby
authors.affiliation: Cancer Program, Broad Institute, Cambridge, Massachusetts3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston Massachusetts.
authors.forename: Chandra
authors.initials: C
authors.lastname: Sekhar Pedamallu
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Mai P
authors.initials: MP
authors.lastname: Hoang
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Sullivan
authors.affiliation: Cancer Program, Broad Institute, Cambridge, Massachusetts.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cherniack
authors.affiliation: Cancer Program, Broad Institute, Cambridge, Massachusetts3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston Massachusetts.
authors.forename: Levi A
authors.initials: LA
authors.lastname: Garraway
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Anat
authors.initials: A
authors.lastname: Stemmer-Rachamimov
authors.affiliation: Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston Massachusetts.
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.affiliation: Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston Massachusetts5Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Priscilla K
authors.initials: PK
authors.lastname: Brastianos
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital, Boston.
authors.forename: William T
authors.initials: WT
authors.lastname: Curry
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital, Boston.
authors.forename: Fred G
authors.initials: FG
authors.lastname: Barker
authors.affiliation: Cancer Program, Broad Institute, Cambridge, Massachusetts3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston Massachusetts.
authors.forename: William C
authors.initials: WC
authors.lastname: Hahn
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital, Boston.
authors.forename: Brian V
authors.initials: BV
authors.lastname: Nahed
authors.affiliation: 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.
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: David N
authors.initials: DN
authors.lastname: Louis
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital, Boston.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Cahill
authors.affiliation: Cancer Program, Broad Institute, Cambridge, Massachusetts3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston Massachusetts7Department of Pathology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D005260:Female; D005629:Frozen Sections; D005910:Glioma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D006801:Humans; D007150:Immunohistochemistry; D007432:Intraoperative Period; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D025202:Molecular Diagnostic Techniques; D060787:Neoplasm Grading; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics*; D013997:Time Factors; D016707:Tissue Fixation
chemical_list: D014408:Biomarkers, Tumor; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; C509186:TERT protein, human; D019098:Telomerase