Radiologic findings and the molecular expression profile of diffuse midline glioma H3 K27M mutant
Abstract
Background
Diffuse midline glioma H3 K27M-mutant (DMG) are reported to show heterogeneous radiologic imaging features in children. We hypothesized that other genetic mutations may contribute to this heterogeneity.
Purpose
To describe the magnetic resonance imaging (MRI) findings of DMG in adult patients and to correlate the imaging findings with the molecular expression profile.
Material and Methods
Eighteen patients with pathologically proven DMG were enrolled. On preoperative MRI, the following were evaluated: location; size of the lesion; ratio of non-enhancing (NE) and contrast-enhancing (CE) area; presence of cortical invasion and necrotic component; maximum relative cerebral blood volume ratio (rCBV ratio) of NE and CE portions; and minimum apparent diffusion coefficient (ADC) of NE and CE portions, among others. Molecular profiles including ATRX expression and p53 mutation were reviewed to find correlation with imaging features.
Results
Thalamus was the most commonly involved location, followed by pons and tectum. Five patients showed loss of normal ATRX expression. p53 mutation was positive in 12 patients. 40% of normal ATRX expression patients had cortical involvement and 20% had leptomeningeal seeding; none of the patients with ATRX loss had cortical involvement or leptomeningeal seeding. Patients with normal ATRX expression showed significantly higher rCBV ratio and lower ADC value in the NE area than patients with ATRX loss (P=0.04, 0.016). p53 mutation status did not correlate with any imaging finding.
Conclusion
Cortical invasion, leptomeningeal tumor spread, lower ADC value and higher rCBV ratio in NE areas of DMG may be related to normal expression of ATRX.
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References
1. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016; 131:803–820.
2. Hawkins C, Ellison DW, Sturm D. Diffuse midline glioma, H3 K27M-mutant In: Louis DN, Ohgaki H, Wiestler OD, et al. editors. WHO classification of tumours of the central nervous system. 4th ed. Lyon: IARC Press, 2016:57–59.
3. Buczkowicz P, Hoeman C, Rakopoulos P, et al. Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nat Genet 2014; 46:451–456.
4. Khuong-Quang DA, Buczkowicz P, Rakopoulos P, et al. K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol 2012; 124:439–447.
5. Jansen MH, Veldhuijzen van Zanten SE, Sanchez Aliaga E, et al. Survival prediction model of children with diffuse intrinsic pontine glioma based on clinical and radiological criteria. Neuro Oncol 2015; 17:160–166.
6. Shows J, Marshall C, Perry A, et al. Genetics of glioblastomas in rare anatomical locations: spinal cord and optic nerve. Brain Pathol 2016; 26:120–123.
7. Kleinschmidt-DeMasters BK, Mulcahy Levy JM. H3 K27M-mutant gliomas in adults vs. children share similar histological features and adverse prognosis. Clin Neuropathol 2018; 37:53–63.
8. Aboian MS, Solomon DA, Felton E, et al. Imaging characteristics of pediatric diffuse midline gliomas with histone H3 K27M mutation. AJNR Am J Neuroradiol 2017; 38:795–800.
9. Solomon DA, Wood MD, Tihan T, et al. Diffuse midline gliomas with histone H3-K27M mutation: a series of 47 cases assessing the spectrum of morphologic variation and associated genetic alterations. Brain Pathol 2016; 26:569–580.
10. Case AJ, Domann FE. Absence of manganese superoxide dismutase delays p53-induced tumor formation. Redox Biol 2014; 2:220–223.
11. Jin Y, Xiao W, Song T, et al. Expression and prognostic significance of p53 in glioma patients: a meta-analysis. Neurochem Res 2016; 41:1723–1731.
12. Argentaro A, Yang JC, Chapman L, et al. Structural consequences of disease-causing mutations in the ATRX-DNMT3-DNMT3L (ADD) domain of the chromatin-associated protein ATRX. Proc Natl Acad Sci U S A 2007; 104:11939–11944.
13. Cai J, Zhu P, Zhang C, et al. Detection of ATRX and IDH1-R132H immunohistochemistry in the progression of 211 paired gliomas. Oncotarget 2016; 7:16384–16395.
14. Wiestler B, Capper D, Holland-Letz T, et al. ATRX loss refines the classification of anaplastic gliomas and identifies a subgroup of IDH mutant astrocytic tumors with better prognosis. Acta Neuropathol 2013; 126:443–451.
15. Lewis PW, Elsaesser SJ, Noh KM, et al. Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres. Proc Natl Acad Sci U S A 2010; 107:14075–14080.
16. Abedalthagafi M, Phillips JJ, Kim GE, et al. The alternative lengthening of telomere phenotype is significantly associated with loss of ATRX expression in high-grade pediatric and adult astrocytomas: a multi-institutional study of 214 astrocytomas. Mod Pathol 2013; 26:1425–1432.
17. Heaphy CM, Subhawong AP, Hong SM, et al. Prevalence of the alternative lengthening of telomeres telomere maintenance mechanism in human cancer subtypes. Am J Pathol 2011; 179:1608–1615.
18. Cai J, Chen J, Zhang W, et al. Loss of ATRX, associated with DNA methylation pattern of chromosome end, impacted biological behaviors of astrocytic tumors. Oncotarget 2015; 6:18105–18115.
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Article first published online: November 11, 2020
Issue published: October 2021
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PubMed: 33175579
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