Case Reports

. 2020 Mar 20;8(1):37.

doi: 10.1186/s40478-020-00905-w.

Diffuse intrinsic pontine glioma-like tumor with EZHIP expression and molecular features of PFA ependymoma

Drew Pratt¹, Martha Quezado², Zied Abdullaev², Debra Hawes³, Fusheng Yang³, Hugh J L Garton⁴, Alexander R Judkins³, Rajen Mody⁵, Arul Chinnaiyan^{1

6}, Kenneth Aldape², Carl Koschmann^{7

8}, Sriram Venneti^{9

10}

Affiliations

¹ Laboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, 3520E MSRB 1, 1150 W. Medical Center, Ann Arbor, MI, 48109, USA.
² Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
³ Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine University of Southern California, Los Angeles, CA, USA.
⁴ Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
⁵ Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor, MI, USA.
⁶ Michigan Center for Translational Pathology, Ann Arbor, MI, USA.
⁷ Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor, MI, USA. ckoschma@med.umich.edu.
⁸ Department of Pediatrics, Division of Pediatric Hematology/Oncology, C.S. Mott Children's Hospital at the University of Michigan, 1500 E Medical Center Dr., Ann Arbor, MI, 48109, USA. ckoschma@med.umich.edu.
⁹ Laboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, 3520E MSRB 1, 1150 W. Medical Center, Ann Arbor, MI, 48109, USA. svenneti@med.umich.edu.
¹⁰ Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor, MI, USA. svenneti@med.umich.edu.

PMID: 32197665
PMCID: PMC7083001
DOI: 10.1186/s40478-020-00905-w

Case Reports

Diffuse intrinsic pontine glioma-like tumor with EZHIP expression and molecular features of PFA ependymoma

Drew Pratt et al. Acta Neuropathol Commun. 2020.

. 2020 Mar 20;8(1):37.

doi: 10.1186/s40478-020-00905-w.

Authors

Affiliations

¹ Laboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, 3520E MSRB 1, 1150 W. Medical Center, Ann Arbor, MI, 48109, USA.
² Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
³ Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine University of Southern California, Los Angeles, CA, USA.
⁴ Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
⁵ Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor, MI, USA.
⁶ Michigan Center for Translational Pathology, Ann Arbor, MI, USA.
⁷ Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor, MI, USA. ckoschma@med.umich.edu.
⁸ Department of Pediatrics, Division of Pediatric Hematology/Oncology, C.S. Mott Children's Hospital at the University of Michigan, 1500 E Medical Center Dr., Ann Arbor, MI, 48109, USA. ckoschma@med.umich.edu.
⁹ Laboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, 3520E MSRB 1, 1150 W. Medical Center, Ann Arbor, MI, 48109, USA. svenneti@med.umich.edu.
¹⁰ Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor, MI, USA. svenneti@med.umich.edu.

PMID: 32197665
PMCID: PMC7083001
DOI: 10.1186/s40478-020-00905-w

No abstract available

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

**Fig. 1**
Representative MRI characteristics. T1-weighted sagittal image showed an infiltrative mass centered within and expanding the pons (a). The exophytic portion of the tumor is seen encasing the basilar artery (b). The mass demonstrated classic MR characteristics of DIPG including increased T2 (c) and FLAIR (d) signals, and lack of post contrast enhancement (e)

**Fig. 2**
Histopathology and results of integrative sequencing and array-based methylation profiling. Routine H&E sections showed a high-grade cellular tumor (a). Tumor cells were seen infiltrating axons (b). H3K27M stain was negative (with appropriate control staining) and H3K27me3 showed loss with expression in admixed non-neoplastic cells (c, d). Copy number profiling through MI-ONCOSEQ mainly showed whole-arm changes including gains in 1q, 7p, 17p, and losses of 13q and partial 13p (e). Gene expression (RNA-seq) showed high expression of *EZHIP* (*CXorf67*) (f, expression is presented as log-transformed fragments per kilobase of exon model per million reads mapped, or FPKM, and shown as a percentile rank among the MI-ONCOSEQ compendium). Immunohistochemistry confirmed EZHIP protein overexpression and loss of Olig2 in tumor cells (f). Reproduction of the unsupervised clustering analysis of reference and diagnostic cohorts by Capper et al. [3] using t-Distributed Stochastic Neighbor Embedding (t-SNE), with incorporation of the presented case (g). Reproduction of the Consensus Clustering analysis by Pajtler et al. [11] and incorporation of our case showing clustering with the PFA-1c subtype (h). Heatmap representation and clustering were performed identically to the previously published methods [11]. Illustration of the previously defined [11] Consensus Clustering-based PFA major subgroups and minor subtypes (n = 675) using t-SNE dimensionality reduction (i); arrowhead denotes placement of the current case. Scale bars = 40 μm

See this image and copyright information in PMC

Comment in

Autopsy findings of previously described case of diffuse intrinsic pontine glioma-like tumor with EZHIP expression and molecular features of PFA ependymoma.
Alturkustani M, Cotter JA, Mahabir R, Hawes D, Koschmann C, Venneti S, Judkins AR, Szymanski LJ. Alturkustani M, et al. Acta Neuropathol Commun. 2021 Jun 23;9(1):113. doi: 10.1186/s40478-021-01215-5. Acta Neuropathol Commun. 2021. PMID: 34162441 Free PMC article. No abstract available.

References

1. Albright AL, Packer RJ, Zimmerman R, Rorke LB, Boyett J, Hammond GD. Magnetic resonance scans should replace biopsies for the diagnosis of diffuse brain stem gliomas: a report from the Children's Cancer group. Neurosurgery. 1993;33:1026–1029. doi: 10.1227/00006123-199312000-00010. - DOI - PubMed
1. Bayliss J, Mukherjee P, Lu C, Jain SU, Chung C, Martinez D, Sabari B, Margol AS, Panwalkar P, Parolia A, et al. Lowered H3K27me3 and DNA hypomethylation define poorly prognostic pediatric posterior fossa ependymomas. Sci Transl Med. 2016;8:366ra161. doi: 10.1126/scitranslmed.aah6904. - DOI - PMC - PubMed
1. Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D, Koelsche C, Sahm F, Chavez L, Reuss DE, et al (2018) DNA methylation-based classification of central nervous system tumours. Nature 555: 469–474 Doi 10.1038/nature26000 - PMC - PubMed
1. Gupta N, Goumnerova LC, Manley P, Chi SN, Neuberg D, Puligandla M, Fangusaro J, Goldman S, Tomita T, Alden T, et al. Prospective feasibility and safety assessment of surgical biopsy for patients with newly diagnosed diffuse intrinsic pontine glioma. Neuro-Oncology. 2018;20:1547–1555. doi: 10.1093/neuonc/noy070. - DOI - PMC - PubMed
1. Harutyunyan AS, Krug B, Chen H, Papillon-Cavanagh S, Zeinieh M, De Jay N, Deshmukh S, Chen CCL, Belle J, Mikael LG, et al. H3K27M induces defective chromatin spread of PRC2-mediated repressive H3K27me2/me3 and is essential for glioma tumorigenesis. Nat Commun. 2019;10:1262. doi: 10.1038/s41467-019-09140-x. - DOI - PMC - PubMed

Publication types

Actions
Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions

LinkOut - more resources

Full Text Sources

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Diffuse intrinsic pontine glioma-like tumor with EZHIP expression and molecular features of PFA ependymoma

Affiliations

Diffuse intrinsic pontine glioma-like tumor with EZHIP expression and molecular features of PFA ependymoma

Authors

Affiliations

Conflict of interest statement

Figures

Comment in

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources