Details of Disease

General Information of Disease (ID: DISUMRNZ)

• Disease Name: Ependymoma
• Synonyms: papillary ependymoma (histologic variant); clear cell ependymoma (histologic variant); ependymoma, familial; tanycytic ependymoma (histologic variant); WHO grade II ependymal neoplasm; WHO grade II ependymal tumor; WHO grade II ependymal tumour; ependymoma, benign; epithelial ependymoma; benign ependymoma; ependymoma
• Disease Class: 2A00: Brain cancer
• Definition: A WHO grade II, slow growing tumor of children and young adults, usually located intraventricularly. It is the most common ependymal neoplasm. It often causes clinical symptoms by blocking cerebrospinal fluid pathways. Key histological features include perivascular pseudorosettes and ependymal rosettes. (WHO)
• Disease Hierarchy:
  DISYUEIO: Ependymal tumor
  DIS9NNT0: Grade II glioma
  DISUMRNZ: Ependymoma
• ICD Code:
  ICD-11: ICD-11: 2A00.0Y
  Expand ICD-11: '2A00.0Y
• Disease Identifiers:
  MONDO ID: MONDO_0016698
  MESH ID: D004806
  UMLS CUI: C0014474
  MedGen ID: 41825
  HPO ID: HP:0002888
  Orphanet ID: 251636
  SNOMED CT ID: 1186904005

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Erlotinib	DMCMBHA	Approved	Small molecular drug	[1]

This Disease is Treated as An Indication in 2 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
EGFR806-specific CAR T cell	DM3AD65	Phase 1	CAR T Cell Therapy	[2]
HER2-specific CAR T cell	DMJKBWO	Phase 1	CAR T Cell Therapy	[3]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 17 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
EPHB2	TTKPV6O	moderate	Biomarker	[4]
GDNF	TTF23ML	Strong	Biomarker	[5]
HOXB13	TTZ6I58	Strong	Biomarker	[6]
HTR1B	TTK8CXU	Strong	Biomarker	[7]
IDH1	TTV2A1R	Strong	Altered Expression	[8]
L1CAM	TTC9D3K	Strong	Biomarker	[9]
MYCN	TT9JBY5	Strong	Genetic Variation	[10]
NCL	TTK1V5Q	Strong	Biomarker	[11]
PTPRS	TTCWXFA	Strong	Biomarker	[12]
RTBDN	TT9F4MC	Strong	Biomarker	[13]
SIK1	TT1H6LC	Strong	Altered Expression	[14]
TTR	TTPOYU7	Strong	Altered Expression	[12]
YAP1	TT8UN2D	Strong	Biomarker	[15]
JAG2	TTOJY1B	Definitive	Altered Expression	[16]
MKI67	TTB4UNG	Definitive	Altered Expression	[17]
S1PR3	TTDYP7I	Definitive	Biomarker	[18]
VEGFB	TTPJQHE	Definitive	Biomarker	[19]

This Disease Is Related to 41 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
IPO7	OTDFMQ00	Limited	Biomarker	[20]
TSC2	OT47LWI9	Limited	Biomarker	[21]
CAPS	OTC9GZ2M	moderate	Biomarker	[22]
OLIG2	OTMCN6D3	moderate	Biomarker	[23]
ATRX	OT77RSQW	Strong	Biomarker	[24]
BCL7C	OT8P2IFT	Strong	Biomarker	[13]
DCX	OTISR7K3	Strong	Biomarker	[25]
DNAJC15	OTNDUKAA	Strong	Posttranslational Modification	[26]
EZHIP	OTDP2O9X	Strong	Altered Expression	[27]
GLS2	OT08MSHL	Strong	Altered Expression	[28]
HIC1	OTI9TWY4	Strong	Genetic Variation	[29]
LAMA2	OTFROQWE	Strong	Biomarker	[30]
MAMLD1	OT9EVMQY	Strong	Genetic Variation	[31]
RAB3A	OT2GIUO5	Strong	Biomarker	[13]
RELA	OTUJP9CN	Strong	Genetic Variation	[32]
RFX3	OTE0EI8Z	Strong	Altered Expression	[12]
TNFRSF10C	OTVHOL9B	Strong	Biomarker	[33]
ARMC9	OT0MZER2	Definitive	Biomarker	[29]
BEX1	OTBQIF0H	Definitive	Biomarker	[34]
CBY1	OTAKMUS2	Definitive	Altered Expression	[35]
CD151	OTF3UZS7	Definitive	Genetic Variation	[36]
EPB41	OTGCFPV8	Definitive	Altered Expression	[37]
EPB41L3	OTS6CHG2	Definitive	Genetic Variation	[29]
ESX1	OTZUPU2C	Definitive	Genetic Variation	[38]
FOXJ1	OT7LLBZ7	Definitive	Altered Expression	[39]
HES4	OTCGMQDT	Definitive	Altered Expression	[16]
HEY2	OTU4J3ZI	Definitive	Altered Expression	[40]
KIF4A	OT3UWL7D	Definitive	Biomarker	[41]
KRT75	OT28B9E6	Definitive	Biomarker	[42]
LRIG3	OT6TKZTU	Definitive	Altered Expression	[43]
MIB1	OT5C404P	Definitive	Altered Expression	[17]
NELL2	OTS4MJZ7	Definitive	Altered Expression	[44]
NFIC	OTLMCUIB	Definitive	Biomarker	[45]
OTX2	OTTV05B1	Definitive	Biomarker	[46]
RBL2	OTBQSOE6	Definitive	Altered Expression	[47]
S100A2	OTTGHJ1H	Definitive	Biomarker	[48]
SHC3	OT305NPA	Definitive	Biomarker	[18]
TP53INP1	OT2363Z9	Definitive	Biomarker	[49]
TP73	OT0LUO47	Definitive	Genetic Variation	[50]
TPR	OTUBBA4W	Definitive	Biomarker	[35]
TSPAN4	OTKFK57F	Definitive	Genetic Variation	[36]

References

• [1] Erlotinib FDA Label
• [2] ClinicalTrials.gov (NCT03638167) EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors
• [3] ClinicalTrials.gov (NCT03500991) HER2-specific CAR T Cell Locoregional Immunotherapy for HER2-positive Recurrent/Refractory Pediatric CNS Tumors
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• [5] Glial cell-line derived neurotrophic factor (GDNF) family of ligands confer chemoresistance in a ligand-specific fashion in malignant gliomas. J Clin Neurosci. 2009 Mar;16(3):427-36. doi: 10.1016/j.jocn.2008.06.002. Epub 2009 Jan 12.
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• [8] Moderate-to-strong expression of FGFR3 and TP53 alterations in a subpopulation of choroid plexus tumors.Histol Histopathol. 2020 Jul;35(7):673-680. doi: 10.14670/HH-18-180. Epub 2019 Oct 29.
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• [10] MYCN amplification drives an aggressive form of spinal ependymoma.Acta Neuropathol. 2019 Dec;138(6):1075-1089. doi: 10.1007/s00401-019-02056-2. Epub 2019 Aug 14.
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• [14] Rare but Recurrent ROS1 Fusions Resulting From Chromosome 6q22 Microdeletions are Targetable Oncogenes in Glioma.Clin Cancer Res. 2018 Dec 15;24(24):6471-6482. doi: 10.1158/1078-0432.CCR-18-1052. Epub 2018 Aug 31.
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• [18] EDG3 and SHC3 on chromosome 9q22 are co-amplified in human ependymomas.Cancer Lett. 2010 Apr 1;290(1):36-42. doi: 10.1016/j.canlet.2009.08.023. Epub 2009 Sep 12.
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• [20] Genomics and epigenetics: A study of ependymomas in pediatric patients.Clin Neurol Neurosurg. 2016 May;144:53-8. doi: 10.1016/j.clineuro.2016.02.041. Epub 2016 Mar 5.
• [21] Reduced TSC2 RNA and protein in sporadic astrocytomas and ependymomas.Ann Neurol. 1997 Aug;42(2):230-5. doi: 10.1002/ana.410420215.
• [22] Identification of novel biomarkers in pediatric primitive neuroectodermal tumors and ependymomas by proteome-wide analysis.J Neuropathol Exp Neurol. 2007 Jun;66(6):505-16. doi: 10.1097/01.jnen.0000240475.35414.c3.
• [23] SOX10 and Olig2 as negative markers for the diagnosis of ependymomas: An immunohistochemical study of 98 glial tumors.Histol Histopathol. 2016 Jan;31(1):95-102. doi: 10.14670/HH-11-654. Epub 2015 Aug 19.
• [24] NF2 and ATRX gene copy number losses on a case of ovarian ependymoma.Hum Pathol. 2019 Jan;83:204-211. doi: 10.1016/j.humpath.2018.06.019. Epub 2018 Jun 23.
• [25] Expression of doublecortin in tumours of the central and peripheral nervous system and in human non-neuronal tissues.Acta Neuropathol. 2006 Mar;111(3):247-54. doi: 10.1007/s00401-006-0038-z. Epub 2006 Mar 7.
• [26] Epigenetic inactivation of MCJ (DNAJD1) in malignant paediatric brain tumours.Int J Cancer. 2006 Jan 15;118(2):346-52. doi: 10.1002/ijc.21353.
• [27] EZHIP/CXorf67 mimics K27M mutated oncohistones and functions as an intrinsic inhibitor of PRC2 function in aggressive posterior fossa ependymoma.Neuro Oncol. 2019 Jul 11;21(7):878-889. doi: 10.1093/neuonc/noz058.
• [28] Relative expression of mRNAS coding for glutaminase isoforms in CNS tissues and CNS tumors.Neurochem Res. 2008 May;33(5):808-13. doi: 10.1007/s11064-007-9507-6. Epub 2007 Oct 17.
• [29] Genetic differences on intracranial versus spinal cord ependymal tumors: a meta-analysis of genetic researches.Eur Spine J. 2016 Dec;25(12):3942-3951. doi: 10.1007/s00586-016-4745-4. Epub 2016 Sep 16.
• [30] Laminin alpha 2 enables glioblastoma stem cell growth.Ann Neurol. 2012 Nov;72(5):766-78. doi: 10.1002/ana.23674.
• [31] Childhood supratentorial ependymomas with YAP1-MAMLD1 fusion: an entity with characteristic clinical, radiological, cytogenetic and histopathological features.Brain Pathol. 2019 Mar;29(2):205-216. doi: 10.1111/bpa.12659. Epub 2018 Nov 11.
• [32] The TP53 p.R337H mutation is uncommon in a Brazilian cohort of pediatric patients diagnosed with ependymoma.Neurol Sci. 2020 Mar;41(3):691-694. doi: 10.1007/s10072-019-04112-x. Epub 2019 Nov 14.
• [33] Pediatric supratentorial ependymomas show more frequent deletions on chromosome 9 than infratentorial ependymomas: a microsatellite analysis.Cancer Genet Cytogenet. 2009 Jun;191(2):90-6. doi: 10.1016/j.cancergencyto.2009.02.010.
• [34] Epigenetic genome-wide analysis identifies BEX1 as a candidate tumour suppressor gene in paediatric intracranial ependymoma.Cancer Lett. 2014 Apr 28;346(1):34-44. doi: 10.1016/j.canlet.2013.12.005. Epub 2013 Dec 11.
• [35] Real-time quantitative PCR analysis of pediatric ependymomas identifies novel candidate genes including TPR at 1q25 and CHIBBY at 22q12-q13.Genes Chromosomes Cancer. 2008 Nov;47(11):1005-22. doi: 10.1002/gcc.20607.
• [36] Novel fusion genes and chimeric transcripts in ependymal tumors.Genes Chromosomes Cancer. 2016 Dec;55(12):944-953. doi: 10.1002/gcc.22392. Epub 2016 Jul 28.
• [37] Alterations of protein 4.1 family members in ependymomas: a study of 84 cases.Mod Pathol. 2005 Jul;18(7):991-7. doi: 10.1038/modpathol.3800390.
• [38] Genomic Landscape of Intramedullary Spinal Cord Gliomas.Sci Rep. 2019 Dec 10;9(1):18722. doi: 10.1038/s41598-019-54286-9.
• [39] Decreased FOXJ1 expression and its ciliogenesis programme in aggressive ependymoma and choroid plexus tumours.J Pathol. 2016 Mar;238(4):584-97. doi: 10.1002/path.4682.
• [40] Study of chromosome 9q gain, Notch pathway regulators and Tenascin-C in ependymomas.J Neurooncol. 2014 Jan;116(2):267-74. doi: 10.1007/s11060-013-1287-z. Epub 2013 Nov 1.
• [41] Identification of biomarkers and construction of a microRNA-mRNA regulatory network for ependymoma using integrated bioinformatics analysis.Oncol Lett. 2019 Dec;18(6):6079-6089. doi: 10.3892/ol.2019.10941. Epub 2019 Sep 30.
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• [43] Expression of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins in human ependymoma relates to tumor location, WHO grade, and patient age.Clin Neuropathol. 2009 Jan-Feb;28(1):21-7. doi: 10.5414/npp28021.
• [44] Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma.Acta Neuropathol Commun. 2016 Aug 22;4(1):88. doi: 10.1186/s40478-016-0349-9.
• [45] YAP1 subgroup supratentorial ependymoma requires TEAD and nuclear factor I-mediated transcriptional programmes for tumorigenesis.Nat Commun. 2019 Sep 2;10(1):3914. doi: 10.1038/s41467-019-11884-5.
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