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Elevated Citrate Levels and Histone H3K27M mutations in Pediatric Midline Gliomas-Predictors of Adverse Outcome
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  • Chenue Abongwa,
  • Benita Tamrazi,
  • stefan bluml,
  • Fusheng Yang,
  • Debra Hawes,
  • Nathan Robison,
  • Girish Dhall
Chenue Abongwa
Children's Hospital Los Angeles Department of Hematology and Oncology
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Benita Tamrazi
Children's Hospital Los Angeles
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stefan bluml
USC/Childrens Hospital Los Angeles
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Fusheng Yang
Children's Hospital of Los Angeles
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Debra Hawes
Children's Hospital Los Angeles
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Nathan Robison
Children's Hospital Los Angeles, University of Southern California Keck School of Medicine
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Girish Dhall
University of Alabama at Birmingham
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Abstract

Background: Low Grade Gliomas(LGG) account for about 50% of childhood brain tumors. Elevated citrate levels have previously been shown to be markers for aggressive behavior in LGGs and the H3K27M and G34R/V mutations have emerged as molecular drivers for pediatric high-grade gliomas(HGG). Procedure: We retrospectively analyzed data from 25 patients with midline gliomas to determine whether citrate levels measured through magnetic resonance spectroscopy(MRS) were associated with histone mutations identified by immunohistochemistry. Results: Median age was 6 years (range:0-16 years) with 13 males and 12 females. Most of the patients 14(56%) had a LGG with the most common locations being the thalamus 13(52%) and brainstem 7(28%). The majority had undergone a biopsy 16(65%) or a partial resection 8(32%). Gross total resection was achieved in only one patient(4%). The majority of the patients received adjuvant chemotherapy and/or radiotherapy. Median citrate levels trended higher in patients with HGG compared to those with LGG (1.49vs0.93mmol/kg, p-value=0.16) and in patients with the H3K27M mutation compared to those without (2.30vs0.80mmol/kg, p-value 0.26). Histological grading (LGGvsHGG) (OR: 3.96, 95% confidence interval (CI):1.32-11.94), H3K27M mutation (OR:3.77, 95% CI:1.05-13.61), and age (OR:1.12, 95%CI:1.00-1.25) were significant adverse prognostic factors in univariate analysis but only the histological grading remained significant in multivariate analysis. Conclusion: We determined that H3K27M mutations and elevated citrate levels were adverse prognostic factors in both patients with LGG and HGG. Exploring the relation between these two markers in larger studies could lead to a noninvasive way of predicting high risk behavior prior to biopsy.