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Clinical implications of molecular analysis in diffuse glioma stratification

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Abstract

The revised 4th edition of the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO) has introduced the integrated diagnostic classification that combines molecular and histological diagnoses for diffuse gliomas. In this study, we evaluated the molecular alterations for consecutive 300 diffuse glioma cases (grade 2, 56; grade 3, 62; grade 4, 182) based on this classification. Mutations in the isocitrate dehydrogenase (IDH) genes were common in lower grade glioma (LGG: grade2–3), and when combined with 1p/19q status, LGGs could be stratified into three groups except for four cases (Astrocytoma, IDH-mutant: 44; Oligodendroglioma, IDH-mutant and 1p/19q codeleted: 37; Astrocytoma, IDH-wildtype: 33). 1p/19q-codeleted oligodendrogliomas were clinically the most favorable subgroup even with upfront chemotherapy. In contrast, IDH-wildtype astrocytomas had a relatively worse prognosis; however, this subgroup was more heterogeneous. Of this subgroup, 11 cases had TERT promoter (pTERT) mutation with shorter overall survival than 12 pTERT-wildtype cases. Additionally, a longitudinal analysis indicated pTERT mutation as early molecular event for gliomagenesis. Therefore, pTERT mutation is critical for the diagnosis of molecular glioblastoma (WHO grade 4), regardless of histological findings, and future treatment strategy should be considered based on the precise molecular analysis.

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Acknowledgements

This study was supported by the Japanese Society for the Promotion of Science Grants-in-Aid for Scientific Research (JSPS KAKENHI) Grant No. JP21H03044, JP21K09128, JP20K09392, JP20K17972, 19K17673, and Fujita Memorial Fund for Medical Research (GAKF800362) and Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care(GAKF800381)

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Authors and Affiliations

  1. Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Masahiro Mizoguchi, Nobuhiro Hata, Daisuke Kuga, Ryusuke Hatae, Yojiro Akagi, Yuhei Sangatsuda, Yutaka Fujioka, Kosuke Takigawa & Yusuke Funakoshi

  2. Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Satoshi O. Suzuki & Toru Iwaki

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  1. Masahiro Mizoguchi
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  2. Nobuhiro Hata
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Correspondence to Masahiro Mizoguchi.

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Mizoguchi, M., Hata, N., Kuga, D. et al. Clinical implications of molecular analysis in diffuse glioma stratification. Brain Tumor Pathol 38, 210–217 (2021). https://doi.org/10.1007/s10014-021-00409-y

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