Myxoid glioneuronal tumor of the septum pellucidum and lateral ventricle is defined by a recurrent PDGFRA p.K385 mutation and DNT-like methylation profile

David A Solomon^{1

2}, Andrey Korshunov^{3

4}, Martin Sill^{5

6

7}, David T W Jones^{5

6}, Marcel Kool^{5

6}, Stefan M Pfister^{5

6

7}, Xuemo Fan⁸, Serguei Bannykh⁸, Jethro Hu⁹, Moise Danielpour¹⁰, Rong Li¹¹, James Johnston¹², Elaine Cham¹³, Tabitha Cooney¹⁴, Peter P Sun¹⁵, Nancy Ann Oberheim Bush¹⁶, Michael McDermott¹⁷, Jessica Van Ziffle^{18

19}, Courtney Onodera^{18

19}, James P Grenert^{18

19}, Boris C Bastian^{18

19}, Javier E Villanueva-Meyer²⁰, Melike Pekmezci¹⁸, Andrew W Bollen¹⁸, Arie Perry^{18

17}

Affiliations

¹ Department of Pathology, University of California, San Francisco, CA, USA. david.solomon@ucsf.edu.
² Clinical Cancer Genomics Laboratory, University of California, San Francisco, CA, USA. david.solomon@ucsf.edu.
³ Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
⁴ Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁵ Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
⁶ Division of Pediatric Neuro-Oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁷ Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.
⁸ Department of Pathology, Cedars Sinai Medical Center, Los Angeles, CA, USA.
⁹ Department of Neurology, Cedars Sinai Medical Center, Los Angeles, CA, USA.
¹⁰ Department of Neurosurgery, Cedars Sinai Medical Center, Los Angeles, CA, USA.
¹¹ Department of Pathology, Children's Hospital of Alabama, Birmingham, AL, USA.
¹² Department of Neurosurgery, Children's Hospital of Alabama, Birmingham, AL, USA.
¹³ Department of Pathology, UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
¹⁴ Department of Hematology/Oncology, UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
¹⁵ Department of Neurological Surgery, UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
¹⁶ Division of Neuro-Oncology, Department of Neurological Surgery, University of California, San Francisco, CA, USA.
¹⁷ Department of Neurological Surgery, University of California, San Francisco, CA, USA.
¹⁸ Department of Pathology, University of California, San Francisco, CA, USA.
¹⁹ Clinical Cancer Genomics Laboratory, University of California, San Francisco, CA, USA.
²⁰ Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.

PMID: 30006677
PMCID: PMC7787982
DOI: 10.1007/s00401-018-1883-2

Myxoid glioneuronal tumor of the septum pellucidum and lateral ventricle is defined by a recurrent PDGFRA p.K385 mutation and DNT-like methylation profile

David A Solomon et al. Acta Neuropathol. 2018 Aug.

. 2018 Aug;136(2):339-343.

doi: 10.1007/s00401-018-1883-2. Epub 2018 Jul 13.

Authors

Affiliations

¹ Department of Pathology, University of California, San Francisco, CA, USA. david.solomon@ucsf.edu.
² Clinical Cancer Genomics Laboratory, University of California, San Francisco, CA, USA. david.solomon@ucsf.edu.
³ Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
⁴ Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁵ Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
⁶ Division of Pediatric Neuro-Oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁷ Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.
⁸ Department of Pathology, Cedars Sinai Medical Center, Los Angeles, CA, USA.
⁹ Department of Neurology, Cedars Sinai Medical Center, Los Angeles, CA, USA.
¹⁰ Department of Neurosurgery, Cedars Sinai Medical Center, Los Angeles, CA, USA.
¹¹ Department of Pathology, Children's Hospital of Alabama, Birmingham, AL, USA.
¹² Department of Neurosurgery, Children's Hospital of Alabama, Birmingham, AL, USA.
¹³ Department of Pathology, UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
¹⁴ Department of Hematology/Oncology, UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
¹⁵ Department of Neurological Surgery, UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
¹⁶ Division of Neuro-Oncology, Department of Neurological Surgery, University of California, San Francisco, CA, USA.
¹⁷ Department of Neurological Surgery, University of California, San Francisco, CA, USA.
¹⁸ Department of Pathology, University of California, San Francisco, CA, USA.
¹⁹ Clinical Cancer Genomics Laboratory, University of California, San Francisco, CA, USA.
²⁰ Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.

PMID: 30006677
PMCID: PMC7787982
DOI: 10.1007/s00401-018-1883-2

No abstract available

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Conflict of interest statement

Conflict of interest

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

Figures

**Figure 1.**
Myxoid glioneuronal tumor of the septum pellucidum and lateral ventricle is defined by a recurrent *PDGFRA* p.K385 hotspot mutation. a, Table of the clinicopathologic features of the four patients with MGNT of SP/LV and the identified *PDGFRA* mutations. b, Pre-operative magnetic resonance imaging for patients #1–3. c, Tumor histology of cases #1–3. Hematoxylin and eosin staining, 40x magnification. d, Snapshot from the Integrated Genome Viewer showing sequencing reads containing a dinucleotide substitution at codon p.K385 of the *PDGFRA* gene in all four cases. Reference transcript NM_006206.

**Figure 2.**
Myxoid glioneuronal tumor of the septum pellucidum and lateral ventricle is defined by a DNT-like methylation profile. Unsupervised clustering of DNA methylation patterns for the four MGNT of SP/LV (black circles numbered 1 through 4), alongside 300 previously characterized glial and neuronal neoplasms. Shown is a two-dimensional representation of pairwise sample correlations using the 10,000 most variably methylated probes by t-distributed stochastic neighbor embedding (tSNE) dimensionality reduction. Reference methylation classes are: ANA PA, anaplastic pilocytic astrocytoma. CN, central neurocytoma. LGG DIG/DIA, desmoplastic infantile ganglioglioma/astrocytoma. LGG DNT, dysembyroplastic neuroepithelial tumor. LGG GG, ganglioglioma. LGG MYB, low grade glioma with *MYB* or *MYBL1* rearrangement. LGG PA MID, midline pilocytic astrocytoma. LGG PA PF, posterior fossa pilocytic astrocytoma. LGG PA/GG ST, supratentorial/hemispheric pilocytic astrocytoma and ganglioglioma. LGG RGNT, rosette-forming glioneuronal tumor.

See this image and copyright information in PMC

References

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1. Gessi M, Hattingen E, Dorner E et al. (2016) Dysembryoplastic neuroepithelial tumor of the septum pellucidum and the supratentorial midline: histopathologic, neuroradiologic, and molecular features of 7 cases. Am J Surg Pathol 40:806–811 - PubMed

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Myxoid glioneuronal tumor of the septum pellucidum and lateral ventricle is defined by a recurrent PDGFRA p.K385 mutation and DNT-like methylation profile

Affiliations

Myxoid glioneuronal tumor of the septum pellucidum and lateral ventricle is defined by a recurrent PDGFRA p.K385 mutation and DNT-like methylation profile

Authors

Affiliations

Conflict of interest statement

Figures

References

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LinkOut - more resources

Other Literature Sources

Research Materials