Dataset Information

Rapid Intraoperative Molecular Characterization of Glioma.

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.

SUBMITTER: Shankar GM

PROVIDER: S-EPMC4872045 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Publications

Rapid Intraoperative Molecular Characterization of Glioma.

Shankar Ganesh M GM Francis Joshua M JM Rinne Mikael L ML Ramkissoon Shakti H SH Huang Franklin W FW Venteicher Andrew S AS Akama-Garren Elliot H EH Kang Yun Jee YJ Lelic Nina N Kim James C JC Brown Loreal E LE Charbonneau Sarah K SK Golby Alexandra J AJ Sekhar Pedamallu Chandra C Hoang Mai P MP Sullivan Ryan J RJ Cherniack Andrew D AD Garraway Levi A LA Stemmer-Rachamimov Anat A Reardon David A DA Wen Patrick Y PY Brastianos Priscilla K PK Curry William T WT Barker Fred G FG Hahn William C WC Nahed Brian V BV Ligon Keith L KL Louis David N DN Cahill Daniel P DP Meyerson Matthew M

JAMA oncology 20150801 5

<h4>Importance</h4>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).<h4>Obser ...[more]

PMID: 26181761

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Project description:BackgroundMolecular diagnosis is crucial for biomarker-assisted glioma resection and management. However, some limitations of current molecular diagnostic techniques prevent their widespread use intraoperatively. With the unique advantages of ultrasound, this study developed a rapid intraoperative molecular diagnostic method based on ultrasound radio-frequency signals.MethodsWe built a brain tumor ultrasound bank with 169 cases enrolled since July 2020, of which 43483 RF signal patches from 67 cases with a pathological diagnosis of glioma were a retrospective cohort for model training and validation. IDH1 and TERT promoter (TERTp) mutations and 1p/19q co-deletion were detected by next-generation sequencing. We designed a spatial-temporal integration model (STIM) to diagnose the three molecular biomarkers, thus establishing a rapid intraoperative molecular diagnostic system for glioma, and further analysed its consistency with the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5). We tested STIM in 16-case prospective cohorts, which contained a total of 10384 RF signal patches. Two other RF-based classical models were used for comparison. Further, we included 20 cases additional prospective data for robustness test (ClinicalTrials.govNCT05656053).FindingsIn the retrospective cohort, STIM achieved a mean accuracy and AUC of 0.9190 and 0.9650 (95% CI, 0.94-0.99) respectively for the three molecular biomarkers, with a total time of 3 s and a 96% match to WHO CNS5. In the prospective cohort, the diagnostic accuracy of STIM is 0.85 ± 0.04 (mean ± SD) for IDH1, 0.84 ± 0.05 for TERTp, and 0.88 ± 0.04 for 1p/19q. The AUC is 0.89 ± 0.02 (95% CI, 0.84-0.94) for IDH1, 0.80 ± 0.04 (95% CI, 0.71-0.89) for TERTp, and 0.85 ± 0.06 (95% CI, 0.73-0.98) for 1p/19q. Compared to the second best available method based on RF signal, the diagnostic accuracy of STIM is improved by 16.70% and the AUC is improved by 19.23% on average.InterpretationSTIM is a rapid, cost-effective, and easy-to-manipulate AI method to perform real-time intraoperative molecular diagnosis. In the future, it may help neurosurgeons designate personalized surgical plans and predict survival outcomes.FundingA full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Dataset Information

Rapid Intraoperative Molecular Characterization of Glioma.

Importance

Observations

Conclusions and relevance

Publications

Rapid Intraoperative Molecular Characterization of Glioma.

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