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Acta Neuropathologica

, Volume 134, Issue 6, pp 961–963 | Cite as

Diffuse midline gliomas with subclonal H3F3A K27M mutation and mosaic H3.3 K27M mutant protein expression

  • Giselle Y. Lopez
  • Nancy Ann Oberheim Bush
  • Joanna J. Phillips
  • John-Paul Bouffard
  • Yaron A. Moshel
  • Kurt Jaeckle
  • B. K. Kleinschmidt-DeMasters
  • Marc K. Rosenblum
  • Arie Perry
  • David A. Solomon
Correspondence

Diffuse midline gliomas are aggressive tumors centered in midline structures of the brain that most commonly occur in children and young adults [6]. They are genetically defined by the presence of K27M mutation in either the H3F3A or HIST1H3B genes, which encode the histone H3 variants H3.3 and H3.1, respectively [1]. Given their poor prognosis, the 2016 WHO Classification includes “Diffuse midline glioma, H3 K27M-mutant” as a WHO grade IV entity, even in cases where only lower-grade histologic features are present [4]. In all cases reported to date, H3 K27M mutation has been a clonal alteration in all regions of tumors assessed by sequencing, and immunostaining with antibodies against H3 K27M mutant protein has revealed uniform expression in all tumor cells [2, 5, 6]. Thus, it has been hypothesized that H3 K27M mutation is the earliest or initiating genetic alteration during gliomagenesis in these tumors. Here we describe two cases of diffuse midline glioma with subclonal H3F3AK27M...

Notes

Acknowledgements

DAS is supported by NIH Director’s Early Independence Award (DP5 OD021403) and the UCSF Physician-Scientist Scholar Program.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests related to this case report.

Supplementary material

401_2017_1780_MOESM1_ESM.pdf (7.2 mb)
Supplementary material 1 (PDF 7343 kb)

References

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Giselle Y. Lopez
    • 1
  • Nancy Ann Oberheim Bush
    • 2
  • Joanna J. Phillips
    • 1
    • 3
  • John-Paul Bouffard
    • 4
  • Yaron A. Moshel
    • 5
    • 6
  • Kurt Jaeckle
    • 7
  • B. K. Kleinschmidt-DeMasters
    • 8
  • Marc K. Rosenblum
    • 9
  • Arie Perry
    • 1
    • 3
  • David A. Solomon
    • 1
    • 10
  1. 1.Division of Neuropathology, Department of PathologyUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Division of Neuro-Oncology, Department of Neurological SurgeryUniversity of CaliforniaSan FranciscoUSA
  3. 3.Department of Neurological SurgeryUniversity of CaliforniaSan FranciscoUSA
  4. 4.Department of PathologyOverlook Medical CenterSummitUSA
  5. 5.Atlantic Neurosurgical SpecialistsSummitUSA
  6. 6.Department of NeurosurgeryNYU Langone Medical CenterNew YorkUSA
  7. 7.Department of NeurosciencesAtlantic Health SystemSummitUSA
  8. 8.Departments of Pathology, Neurology, and NeurosurgeryUniversity of ColoradoAuroraUSA
  9. 9.Department of PathologyMemorial Sloan Kettering Cancer CenterNew YorkUSA
  10. 10.Clinical Cancer Genomics Laboratory, Department of PathologyUniversity of CaliforniaSan FranciscoUSA

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