Yoko Fujita1, Luis Nunez-Rubiano2, Antonio Dono1, Allison Bellman3, Mauli Shah4, Juan C Rodriguez1, Vasanta Putluri5, Abu Hena Mostafa Kamal5, Nagireddy Putluri5,6, Roy F Riascos2,7, Jay-Jiguang Zhu1,7, Yoshua Esquenazi8,9,10, Leomar Y Ballester11,12. 1. Vivian L. Smith Department of Neurosurgery McGovern Medical School, The University of Texas Health Science Center, 6431 Fannin Street, Houston, TX, 77030, USA. 2. Department of Radiology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA. 3. Department of Pathology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA. 4. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 2130 West Holcombe Boulevard, Houston, TX, 77030, USA. 5. Advanced Technology Core, Metabolomics Core, Baylor College of Medicine, Houston, TX, 77030, USA. 6. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA. 7. Memorial Hermann Hospital-TMC, Houston, TX, 77030, USA. 8. Vivian L. Smith Department of Neurosurgery McGovern Medical School, The University of Texas Health Science Center, 6431 Fannin Street, Houston, TX, 77030, USA. yoshua.esquenazilevy@uth.tmc.edu. 9. Memorial Hermann Hospital-TMC, Houston, TX, 77030, USA. yoshua.esquenazilevy@uth.tmc.edu. 10. Center for Precision Health, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA. yoshua.esquenazilevy@uth.tmc.edu. 11. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd., Unit 85, Houston, TX, 77030, USA. lyballester1@mdanderson.org. 12. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 2130 West Holcombe Boulevard, Houston, TX, 77030, USA. lyballester1@mdanderson.org.
Abstract
INTRODUCTION: We aimed to evaluate IDH1 p.R132H mutation and 2-hydroxyglutarate (2HG) in cerebrospinal fluid (CSF) as biomarkers for patients with IDH-mutant gliomas. METHODS: CSF was collected from patients with infiltrating glioma, and 2HG levels were measured by liquid chromatography-mass spectrometry. IDH1 p.R132H mutant allele frequency (MAF) in CSF-ctDNA was measured by digital droplet PCR (ddPCR). Tumor volume was measured from standard-of-care magnetic resonance images. RESULTS: The study included 48 patients, 6 with IDH-mutant and 42 with IDH-wildtype gliomas, and 57 samples, 9 from the patients with IDH-mutant and 48 from the patients with IDH-wildtype gliomas. ctDNA was detected in 7 of the 9 samples from patients with IDH-mutant glioma, and IDH1 p.R132H mutation was detected in 5 of the 7 samples. The MAF ranged from 0.3 to 39.95%. Total 2HG level, D-2HG level, and D/L-2HG ratio in CSF were significantly higher in patients with IDH-mutant gliomas than in patients with IDH-wildtype gliomas. D-2HG level and D/L-2HG ratio correlated with total tumor volume in patients with IDH-mutant gliomas but not in patients with IDH-wildtype gliomas. CONCLUSION: Our results suggest that detection of IDH1 p.R132H mutation by ddPCR and increased D-2HG level in CSF may help identify IDH-mutant gliomas. Our results also suggest that D-2HG level and D/L-2HG ratio correlate with tumor volume in patients with IDH-mutant gliomas. Further prospective studies with larger cohorts are needed to validate these findings.
INTRODUCTION: We aimed to evaluate IDH1 p.R132H mutation and 2-hydroxyglutarate (2HG) in cerebrospinal fluid (CSF) as biomarkers for patients with IDH-mutant gliomas. METHODS: CSF was collected from patients with infiltrating glioma, and 2HG levels were measured by liquid chromatography-mass spectrometry. IDH1 p.R132H mutant allele frequency (MAF) in CSF-ctDNA was measured by digital droplet PCR (ddPCR). Tumor volume was measured from standard-of-care magnetic resonance images. RESULTS: The study included 48 patients, 6 with IDH-mutant and 42 with IDH-wildtype gliomas, and 57 samples, 9 from the patients with IDH-mutant and 48 from the patients with IDH-wildtype gliomas. ctDNA was detected in 7 of the 9 samples from patients with IDH-mutant glioma, and IDH1 p.R132H mutation was detected in 5 of the 7 samples. The MAF ranged from 0.3 to 39.95%. Total 2HG level, D-2HG level, and D/L-2HG ratio in CSF were significantly higher in patients with IDH-mutant gliomas than in patients with IDH-wildtype gliomas. D-2HG level and D/L-2HG ratio correlated with total tumor volume in patients with IDH-mutant gliomas but not in patients with IDH-wildtype gliomas. CONCLUSION: Our results suggest that detection of IDH1 p.R132H mutation by ddPCR and increased D-2HG level in CSF may help identify IDH-mutant gliomas. Our results also suggest that D-2HG level and D/L-2HG ratio correlate with tumor volume in patients with IDH-mutant gliomas. Further prospective studies with larger cohorts are needed to validate these findings.
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