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Clinical utility of a blood based assay for the detection of IDH1.R132H-mutant gliomas

Author

Listed:
  • Syeda Maheen Batool

    (Harvard Medical School)

  • Ana K. Escobedo

    (Harvard Medical School)

  • Tiffaney Hsia

    (Harvard Medical School)

  • Emil Ekanayake

    (Harvard Medical School)

  • Sirena K. Khanna

    (Harvard Medical School)

  • Austin S. Gamblin

    (Harvard Medical School)

  • Hui Zheng

    (Harvard Medical School)

  • Johan Skog

    (a Bio-Techne Brand)

  • Julie J. Miller

    (Harvard Medical School
    Harvard Medical School)

  • Anat O. Stemmer-Rachamimov

    (Harvard Medical School)

  • Daniel P. Cahill

    (Harvard Medical School)

  • Leonora Balaj

    (Harvard Medical School)

  • Bob S. Carter

    (Harvard Medical School)

Abstract

Glioma represents the most common central nervous system neoplasm in adults. Current classification scheme utilizes molecular alterations, particularly IDH1.R132H, to stratify lesions into distinct prognostic groups. Identification of the single nucleotide variant through traditional tissue biopsy assessment poses procedural risks and does not fully reflect the heterogeneous and evolving tumor landscape. Here, we introduce a liquid biopsy assay, mt-IDH1dx. The blood-based test allows minimally invasive detection of tumor-derived extracellular vesicle RNA using only 2 ml plasma volume. We perform rigorous, blinded validation testing across the study population (n = 133), comprising of IDH1.R132H patients (n = 80), IDH1 wild-type gliomas (n = 44), and age matched healthy controls (n = 9). Results from our plasma testing demonstrate an overall sensitivity of 75.0% (95% CI: 64.1%–84.0%), specificity 88.7% (95% CI: 77.0%–95.7%), positive predictive value 90.9%, and negative predictive value 70.1% compared to the tissue gold standard. In addition to fundamental diagnostic applications, the study also highlights the utility of mt-IDH1dx platform for blood-based monitoring and surveillance, offering valuable prognostic information. Finally, the optimized workflow enables rapid and efficient completion of both tumor tissue and plasma testing in under 4 hours from the time of sampling.

Suggested Citation

  • Syeda Maheen Batool & Ana K. Escobedo & Tiffaney Hsia & Emil Ekanayake & Sirena K. Khanna & Austin S. Gamblin & Hui Zheng & Johan Skog & Julie J. Miller & Anat O. Stemmer-Rachamimov & Daniel P. Cahill, 2024. "Clinical utility of a blood based assay for the detection of IDH1.R132H-mutant gliomas," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51332-7
    DOI: 10.1038/s41467-024-51332-7
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    References listed on IDEAS

    as
    1. Lenny Dang & David W. White & Stefan Gross & Bryson D. Bennett & Mark A. Bittinger & Edward M. Driggers & Valeria R. Fantin & Hyun Gyung Jang & Shengfang Jin & Marie C. Keenan & Kevin M. Marks & Rober, 2009. "Cancer-associated IDH1 mutations produce 2-hydroxyglutarate," Nature, Nature, vol. 462(7274), pages 739-744, December.
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