Skip to main content
SpringerLink
Log in

Differentiation between spinal cord diffuse midline glioma with histone H3 K27M mutation and wild type: comparative magnetic resonance imaging

  • Spinal Neuroradiology
  • Published:
Neuroradiology Aims and scope Submit manuscript

Abstract

Purpose

Diffuse midline glioma with histone H3 K27M mutation is a new entity described in the 2016 update of the World Health Organization Classification of Tumors of the Central Nervous System. The purpose of this study was to evaluate the clinical and imaging characteristics to predict the presence of H3 K27M mutation in spinal cord glioma using a machine learning–based classification model.

Methods

A total of 41 spinal cord glioma patients consisting of 24 H3 K27M mutants and 17 wild types were enrolled in this retrospective study. A total of 17 clinical and radiological features were evaluated. The random forest (RF) model was trained with the clinical and radiological features to predict the presence of H3 K27M mutation. The diagnostic ability of the RF model was evaluated using receiver operating characteristic (ROC) analysis. Area under the ROC curves (AUC) was calculated.

Results

MR imaging features of spinal cord diffuse midline gliomas were heterogeneous. Hemorrhage was the only variable that was able to differentiate H3 K27M mutated tumors from wild-type tumors in univariate analysis (p = 0.033). RF classifier yielded 0.632 classification AUC (95% CI, 0.456–0.808), 63.4% accuracy, 45.8% sensitivity, and 88.2% specificity.

Conclusion

Our findings indicate that clinical and radiological features are associated with H3 K27M mutation status in spinal cord glioma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

References

  1. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131:803–820

    Article  PubMed  Google Scholar 

  2. Castel D, Philippe C, Calmon R, Le Dret L, Truffaux N, Boddaert N et al (2015) Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. Acta Neuropathol 130:815–827

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J et al (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44:251–253

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Aihara K, Mukasa A, Gotoh K, Saito K, Nagae G, Tsuji S, Tatsuno K, Yamamoto S, Takayanagi S, Narita Y, Shibui S, Aburatani H, Saito N (2014) H3F3A K27M mutations in thalamic gliomas from young adult patients. Neuro-Oncology 16:140–146

    Article  PubMed  CAS  Google Scholar 

  5. Buczkowicz P, Bartels U, Bouffet E, Becher O, Hawkins C (2014) Histopathological spectrum of paediatric diffuse intrinsic pontine glioma: diagnostic and therapeutic implications. Acta Neuropathol 128:573–581

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Solomon DA, Wood MD, Tihan T, Bollen AW, Gupta N, Phillips JJ et al (2016) 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 26:569–580

    Article  PubMed  CAS  Google Scholar 

  7. Gessi M, Gielen GH, Dreschmann V, Waha A, Pietsch T (2015) High frequency of H3F3A (K27M) mutations characterizes pediatric and adult high-grade gliomas of the spinal cord. Acta Neuropathol 130:435–437

    Article  PubMed  Google Scholar 

  8. Aboian MS, Solomon DA, Felton E, Mabray MC, Villanueva-Meyer JE, Mueller S, Cha S (2017) Imaging characteristics of pediatric diffuse midline gliomas with histone H3 K27M mutation. AJNR Am J Neuroradiol 38:795–800

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Meyronet D, Esteban-Mader M, Bonnet C, Joly MO, Uro-Coste E, Amiel-Benouaich A, Forest F, Rousselot-Denis C, Burel-Vandenbos F, Bourg V, Guyotat J, Fenouil T, Jouvet A, Honnorat J, Ducray F (2017) Characteristics of H3 K27M-mutant gliomas in adults. Neuro-Oncology 19:1127–1134

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Karikari IO, Nimjee SM, Hodges TR, Cutrell E, Hughes BD, Powers CJ, Mehta AI, Hardin C, Bagley CA, Isaacs RE, Haglund MM, Friedman AH (2011) Impact of tumor histology on resectability and neurological outcome in primary intramedullary spinal cord tumors: a single-center experience with 102 patients. Neurosurgery 68:188–197

    Article  PubMed  Google Scholar 

  11. Gao Y, Feng YY, Yu JH, Li QC, Qiu XS, Wang EH (2018) Diffuse midline gliomas with histone H3-K27M mutation: a rare case with PNET-like appearance and neuropil-like islands. Neuropathology 38:165–170

    Article  PubMed  CAS  Google Scholar 

  12. Bender S, Tang Y, Lindroth AM, Hovestadt V, Jones DT, Kool M et al (2013) Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. Cancer Cell 24:660–672

    Article  PubMed  CAS  Google Scholar 

  13. Chan KM, Fang D, Gan H, Hashizume R, Yu C, Schroeder M, Gupta N, Mueller S, James CD, Jenkins R, Sarkaria J, Zhang Z (2013) The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression. Genes Dev 27:985–990

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Herz HM, Morgan M, Gao X, Jackson J, Rickels R, Swanson SK, Florens L, Washburn MP, Eissenberg JC, Shilatifard A (2014) Histone H3 lysine-to-methionine mutants as a paradigm to study chromatin signaling. Science 345:1065–1070

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Lewis PW, Müller MM, Koletsky MS, Cordero F, Lin S, Banaszynski LA et al (2013) Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma. Science 340:857–861

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Sturm D, Witt H, Hovestadt V, Khuong-Quang DA, Jones DT, Konermann C et al (2012) Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 22:425–437

    Article  PubMed  CAS  Google Scholar 

  17. Yuen BT, Knoepfler PS (2013) Histone H3.3 mutations: a variant path to cancer. Cancer Cell 24:567–574

    Article  PubMed  CAS  Google Scholar 

  18. Khuong-Quang DA, Buczkowicz P, Rakopoulos P, Liu XY, Fontebasso AM, Bouffet E, Bartels U, Albrecht S, Schwartzentruber J, Letourneau L, Bourgey M, Bourque G, Montpetit A, Bourret G, Lepage P, Fleming A, Lichter P, Kool M, von Deimling A, Sturm D, Korshunov A, Faury D, Jones DT, Majewski J, Pfister SM, Jabado N, Hawkins C (2012) K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol 124:439–447

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Strobl C, Boulesteix AL, Zeileis A, Hothorn T (2007) Bias in random forest variable importance measures: illustrations, Sources and a Solution. BMC Bioinf 8(1):25

    Article  CAS  Google Scholar 

  20. Tanaka S, Otani R, Hongo H, Matsuda H, Ikemura M, Nomura M et al (2017) PATH-28. Clinical and genetic characteristics of diffuse midline glioma in the spinal cord. Neuro Oncol 19:vi176-vi176

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiology and Research Institute of Radiological Science, College of Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea

    Jo Sung Jung, Yoon Seong Choi, Sung Soo Ahn & Seung-Koo Lee

  2. Department of Neurosurgery, Yonsei University College of Medicine, Seoul, South Korea

    Seong Yi

  3. Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea

    Se Hoon Kim

Authors
  1. Jo Sung Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoon Seong Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sung Soo Ahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seong Yi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Se Hoon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Seung-Koo Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seung-Koo Lee.

Ethics declarations

Funding

No funding was received for this study.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

Informed consent

For this type of retrospective study formal consent is not required.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jung, J.S., Choi, Y.S., Ahn, S.S. et al. Differentiation between spinal cord diffuse midline glioma with histone H3 K27M mutation and wild type: comparative magnetic resonance imaging. Neuroradiology 61, 313–322 (2019). https://doi.org/10.1007/s00234-019-02154-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00234-019-02154-8

Keywords

Search

Navigation