human stem cell derived neurons

Development of Liquid Biomarkers for Temozolomide Induced Hypermutation in Patients with Glioma


This is a pilot study to develop a liquid biomarker for hypermutation in glioma patients previously treated with the chemotherapy temozolomide. The hypothesis is there are unique RNA or cell-free DNA (cfDNA) features that are associated with hypermutation in CSF or serum of patients with temozolomide-induced hypermutated gliomas. Patients with known hypermutation and those without will undergo lumbar puncture to collect CSF as well as a blood draw for serum, which will then be analyzed for the size, concentration and RNA cargo of extracellular vesicles, and deep sequencing of cfDNA to identify markers of hypermutation. We will then test the concordance of CSF and serum samples to determine the optimal method of liquid biopsy for determination of hypermutation as preliminary data to develop a larger study.

Inclusion Criteria
  1. Ability to understand a written informed consent document, and the willingness to sign it.
  2. Participants must have histologically confirmed glioma (any WHO grade is acceptable).
  3. Patients must have had prior treatment with temozolomide, however, subjects on active treatment with temozolomide can be included if they have stable disease.
  4. Age ≥18 years.
  5. ECOG performance status ≤2 or Karnofsky > 60%
  6. Demonstrates adequate bone marrow function as defined below within 7 days:
    1. Absolute neutrophil count ≥1,500/mcL
    2. Platelets ≥100,000/mcL
  7. For Cohort A, availability of UCSF500, next generation, or whole exome sequencing documenting tumor mutational burden or the presence of “hypermutation.” Cohort B patients do not need to have had prior UCSF500, next generation, or whole exome sequencing.
Exclusion Criteria
  1. Has a history of bleeding disorders that may impact the safety of lumbar puncture.
  2. Patients currently on anticoagulation or blood thinners that cannot be held safely for the lumbar puncture procedure for 24 hours.
  3. Current signs and symptoms of infection or documented infection.
  4. Evidence of elevated intracranial pressureor significant mass effect on the MRI scan

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