IDH1 p.R132H ctDNA and D-2-hydroxyglutarate as CSF biomarkers in patients with IDH-mutant gliomas

Fujita, Yöko; Nunez-Rubiano, Luis; Dono, Antonio; Bellman, Allison; Shah, Mauli; Rodríguez, Juan Carlos; Putluri, Vasanta; Kamal, Abu Hena Mostafa; Putluri, Nagireddy; Riascos, Roy F.; Zhu, Jay‐Jiguang; Esquenazi, Yoshua; Ballester, Leomar Y.

doi:10.1007/s11060-022-04060-1

Cited by 20 publications

(9 citation statements)

References 28 publications

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“…Thankfully, none of our patients have yet experienced a true recurrence of their IDH-mutant glioma. As such, we have not yet been able to independently confirm recent findings of increasing CSF D-2-HG with tumor recurrence in two patients 2 . Nevertheless, our data provide the most complete evidence to date regarding the potential dynamic range of D-2-HG achievable within individual patients for longitudinal monitoring and response assessment.…”

Section: Higher 2-hg Has Been Previously Reported In Csf Of Patients ...contrasting

confidence: 81%

“… Abstract D-2-hydroxyglutarate (D-2-HG) is a well-established oncometabolite of isocitrate dehydrogenase (IDH) mutant gliomas. While prior studies have demonstrated that D-2-HG is elevated in the cerebrospinal fluid (CSF) of patients with IDH-mutant gliomas 1,2 , no study has determined if CSF D-2-HG can provide a plausible method to evaluate therapeutic response. We are obtaining CSF samples from consenting patients during their disease course via intra-operative collection and Ommaya reservoirs.…”

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confidence: 99%

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Cerebrospinal fluid 2-hydroxyglutarate (2-HG) as a monitoring biomarker for IDH-mutant gliomas

Riviere-Cazaux

Lacey

Carlstrom

et al. 2023

Preprint

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D-2-hydroxyglutarate (D-2-HG) is a well-established oncometabolite of isocitrate dehydrogenase (IDH) mutant gliomas. While prior studies have demonstrated that D-2-HG is elevated in the cerebrospinal fluid (CSF) of patients with IDH-mutant gliomas1,2, no study has determined if CSF D-2-HG can provide a plausible method to evaluate therapeutic response. We are obtaining CSF samples from consenting patients during their disease course via intra-operative collection and Ommaya reservoirs. D-2-HG and D/L-2-HG consistently decreased following tumor resection and throughout chemoradiation in patients monitored longitudinally. Our early experience with this strategy demonstrates the potential for intracranial CSF D-2-HG as a monitoring biomarker for IDH-mutant gliomas.

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Section: Higher 2-hg Has Been Previously Reported In Csf Of Patients ...contrasting

confidence: 81%

mentioning

confidence: 99%

Cerebrospinal fluid 2-hydroxyglutarate (2-HG) as a monitoring biomarker for IDH-mutant gliomas

Riviere-Cazaux

Lacey

Carlstrom

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…As such, we have not yet been able to independently confirm recent findings of increasing CSF D-2-HG with tumor recurrence in two patients. 2 Nevertheless, our results provide initial data regarding the potential dynamic range of D-2-HG achievable within individual patients for longitudinal monitoring and response assessment.…”

mentioning

confidence: 85%

“…D-2-hydroxyglutarate (D-2-HG) is a well-established oncometabolite of isocitrate dehydrogenase (IDH) mutant gliomas. While prior studies have demonstrated that D-2-HG is elevated in the cerebrospinal fluid (CSF) of patients with IDH-mutant gliomas, 1 , 2 no study has determined if CSF D-2-HG can provide a plausible method to evaluate therapeutic response. We are obtaining CSF samples during patients’ disease courses via intra-operative collection and Ommaya reservoirs.…”

mentioning

confidence: 99%

Cerebrospinal fluid 2-hydroxyglutarate as a monitoring biomarker for IDH-mutant gliomas

Riviere-Cazaux

Lacey

Carlstrom

et al. 2023

Neuro-Oncology Advances

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“…In recent years, various approaches have been developed, including "liquid biopsies" (nucleic acid extracted from biological fluids such as plasma, urine, and cerebrospinal fluid (CSF)) for detecting the IDH mutation (Satomi et al, 2022); D2HG detection in body fluids; and advanced MRI imaging with specific D2HG detection by magnetic resonance spectroscopy (MRS) (Fujita et al, 2022;Mithraprabhu et al, 2021;Tuna et al, 2022). However, none of them is currently used in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Detection of IDH1 Mutation in cfDNA and Tissue of Adult Diffuse Glioma with Allele-Specific qPCR

Husain

Mishra

Siddiqui

et al. 2023

Asian Pac J Cancer Prev

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Background:The World Health Organization (WHO) classification of central nervous system (CNS) tumors necessitates testing of isocitrate dehydrogenase (IDH) 1/2 gene mutation in patients with adult-type diffuse glioma (ADG) for better disease management. In clinical practice, the testing of IDH1 is primarily achieved using immunohistochemistry (IHC) specific to IDH1-R132, which carries a sensitivity of 80% and specificity of 100%. However, in some cases, non-specific background staining or regional heterogeneity in the protein expression of IDH1 may necessitate confirmatory genetic analysis. Robust and reliable assays are needed for IDH1/2 mutation testing. The aim of the current study was to detect IDH1 mutation in cfDNA and tissue of adult-type diffuse glioma with allele-specific qPCR. Materials and Methods: In the current study, IDH1-R132H mutation was analyzed in tumor tissue with paired cell-free DNA (cfDNA) in patients with ADG (n = 45) using IHC and competitive allele-specific Taqman PCR (CAST-PCR). Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue and matched serum for cfDNA using commercially available kits. CAST-PCR with IHC for the detection of IDH1-R132H mutation was also compared. Results: The IDH1-R132H mutation was detected in 46.67% (21/45) cases and 57.78% (26/45) cases using IHC and allele-specific CAST-PCR. In cfDNA of matched IDH1-mutant FFPE tissue DNA, IDH1-R132H mutation was detected in 11.54% (3/26) using CAST-PCR. The concordance rate for IDH1-R132Hmutation between IHC and CAST-PCR was 80.77% (21/26). Conclusion: The CAST-PCR assay is more precise and sensitive for IDH1-R132Hdetection than traditional IHC, and IDH1-R132H mutation detection using cfDNA may add to the current methods of glioma genomic characterization.

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IDH1 p.R132H ctDNA and D-2-hydroxyglutarate as CSF biomarkers in patients with IDH-mutant gliomas

Cited by 20 publications

References 28 publications

Cerebrospinal fluid 2-hydroxyglutarate (2-HG) as a monitoring biomarker for IDH-mutant gliomas

Cerebrospinal fluid 2-hydroxyglutarate (2-HG) as a monitoring biomarker for IDH-mutant gliomas

Cerebrospinal fluid 2-hydroxyglutarate as a monitoring biomarker for IDH-mutant gliomas

Detection of IDH1 Mutation in cfDNA and Tissue of Adult Diffuse Glioma with Allele-Specific qPCR

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