Details of Disease

General Information of Disease (ID: DISTTVLA)

• Disease Name: Schwannoma
• Synonyms: neurolemmoma; SCHW; schwannoma, benign; schwannoma (WHO grade I); schwannoma; psammomatous schwannoma; peripheral fibroblastoma; neurinoma; neurilemmoma; benign schwannoma; benign neurilemmoma
• Definition: A benign, usually encapsulated slow growing tumor composed of Schwann cells. It affects peripheral and cranial nerves. It recurs infrequently and only rare cases associated with malignant transformation have been reported.
• Disease Hierarchy:
  DISJYLBY: Nerve sheath neoplasm
  DISTBY9Z: Tumour
  DISDZT8F: Benign peripheral nerve sheath tumor
  :
  DISTTVLA: Schwannoma
• Disease Identifiers:
  MONDO ID: MONDO_0002546
  MESH ID: D009442
  UMLS CUI: C0027809
  MedGen ID: 45053
  HPO ID: HP:0100008
  Orphanet ID: 252164
  SNOMED CT ID: 189948006

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 14 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
KSR1	TTHL1TV	Limited	Biomarker	[1]
MAP2K2	TT8H9GB	Limited	Biomarker	[2]
EED	TTFNJ4R	Disputed	Biomarker	[3]
PDGFD	TTSN0GA	moderate	Altered Expression	[4]
RAC1	TT2M9CG	moderate	Biomarker	[5]
TIE1	TTT4236	moderate	Altered Expression	[6]
TNK2	TTIET93	moderate	Altered Expression	[7]
MBP	TT2RY5P	Strong	Altered Expression	[8]
PRKAR1A	TTNAHEX	Strong	Biomarker	[9]
SNCA	TT08OSU	Strong	Biomarker	[10]
WT1	TTZ8UT4	Strong	Therapeutic	[11]
AXL	TTZPY6J	Definitive	Biomarker	[12]
NF2	TTZIK7P	Definitive	Genetic Variation	[13]
PDGFRB	TTI7421	Definitive	Altered Expression	[14]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
ABCA2	DTJ4NEG	moderate	Biomarker	[15]

This Disease Is Related to 24 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
DCAF1	OT3ZDVOE	Limited	Biomarker	[1]
SEMA3F	OTQFMS8S	Limited	Biomarker	[16]
SUZ12	OT655XF8	Disputed	Biomarker	[3]
AGAP2	OTEYO9TM	moderate	Genetic Variation	[17]
ANGPT4	OT881M3K	moderate	Altered Expression	[6]
CTNNA1	OTFC725Z	moderate	Biomarker	[18]
GSDMD	OTH39BKI	moderate	Biomarker	[19]
HARS1	OTHOEOTS	moderate	Altered Expression	[20]
MYOC	OT6DAHNF	moderate	Altered Expression	[21]
NF1	OTC29NHH	moderate	Biomarker	[3]
PDLIM2	OTEURRPD	moderate	Biomarker	[22]
RDX	OTNSYUN6	moderate	Biomarker	[23]
SRSF5	OTC5WP98	moderate	Altered Expression	[20]
THSD7A	OT7249HH	moderate	Biomarker	[24]
BMP3	OTCTI0UW	Strong	Altered Expression	[25]
BMP5	OTC0Y6E0	Strong	Altered Expression	[25]
DCX	OTISR7K3	Strong	Altered Expression	[26]
HGS	OTCYYCAC	Strong	Altered Expression	[20]
LATS1	OTOOCG4R	Strong	Biomarker	[27]
MSH4	OTJZMG1Z	Strong	Genetic Variation	[28]
PMP22	OTXWYWCZ	Strong	Altered Expression	[29]
SIPA1L2	OT8NJE5D	Strong	Biomarker	[29]
SMARCB1	OT2LP7LJ	Strong	Genetic Variation	[30]
SOX10	OTF25ULQ	Definitive	Biomarker	[31]

References

• [1] The scaffold protein KSR1, a novel therapeutic target for the treatment of Merlin-deficient tumors.Oncogene. 2016 Jun 30;35(26):3443-53. doi: 10.1038/onc.2015.404. Epub 2015 Nov 9.
• [2] Preclinical assessment of MEK1/2 inhibitors for neurofibromatosis type 2-associated schwannomas reveals differences in efficacy and drug resistance development.Neuro Oncol. 2019 Mar 18;21(4):486-497. doi: 10.1093/neuonc/noz002.
• [3] PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature. 2014 Oct 9;514(7521):247-51.
• [4] Global expression profile in low grade meningiomas and schwannomas shows upregulation of PDGFD, CDH1 and SLIT2 compared to their healthy tissue.Oncol Rep. 2014 Dec;32(6):2327-34. doi: 10.3892/or.2014.3526. Epub 2014 Oct 3.
• [5] Reduced RAC1 activity inhibits cell proliferation and induces apoptosis in neurofibromatosis type 2(NF2)-associated schwannoma.Neurol Res. 2017 Dec;39(12):1086-1093. doi: 10.1080/01616412.2017.1376494. Epub 2017 Sep 22.
• [6] Expression of angiopoietin-1, 2 and 4 and Tie-1 and 2 in gastrointestinal stromal tumor, leiomyoma and schwannoma.World J Gastroenterol. 2007 Sep 7;13(33):4473-9. doi: 10.3748/wjg.v13.i33.4473.
• [7] miRNA-7 attenuation in Schwannoma tumors stimulates growth by upregulating three oncogenic signaling pathways.Cancer Res. 2011 Feb 1;71(3):852-61. doi: 10.1158/0008-5472.CAN-10-1219. Epub 2010 Dec 13.
• [8] Developing myelin specific promoters for schwannoma gene therapy.J Neurosci Methods. 2019 Jul 15;323:77-81. doi: 10.1016/j.jneumeth.2019.05.007. Epub 2019 May 22.
• [9] Molecular mechanisms promoting the pathogenesis of Schwann cell neoplasms.Acta Neuropathol. 2012 Mar;123(3):321-48. doi: 10.1007/s00401-011-0928-6. Epub 2011 Dec 11.
• [10] Alpha-synuclein immunoreactivity in normal and neoplastic Schwann cells.Acta Neuropathol. 2002 Feb;103(2):145-51. doi: 10.1007/s004010100443. Epub 2001 Oct 18.
• [11] Wilms' tumor gene 1 (WT1) silencing inhibits proliferation of malignant peripheral nerve sheath tumor sNF96.2 cell line.PLoS One. 2014 Dec 4;9(12):e114333. doi: 10.1371/journal.pone.0114333. eCollection 2014.
• [12] Soluble AXL: a possible circulating biomarker for neurofibromatosis type 1 related tumor burden.PLoS One. 2014 Dec 31;9(12):e115916. doi: 10.1371/journal.pone.0115916. eCollection 2014.
• [13] CPI-17 Overexpression and Its Correlation With the NF2 Mutation Spectrum in Sporadic Vestibular Schwannomas.Otol Neurotol. 2020 Jan;41(1):e94-e102. doi: 10.1097/MAO.0000000000002430.
• [14] Clinicopathological variables of sporadic schwannomas of peripheral nerve in 291 patients and expression of biologically relevant markers.J Neurosurg. 2018 Sep;129(3):805-814. doi: 10.3171/2017.2.JNS153004. Epub 2017 Sep 8.
• [15] Expression of ABCA2 protein in human vestibular schwannoma and peripheral nerve.J Neurol Sci. 2005 May 15;232(1-2):59-63. doi: 10.1016/j.jns.2005.01.016.
• [16] Merlin/NF2 regulates angiogenesis in schwannomas through a Rac1/semaphorin 3F-dependent mechanism.Neoplasia. 2012 Feb;14(2):84-94. doi: 10.1593/neo.111600.
• [17] Neurofibromatosis 2 (NF2) tumor suppressor merlin inhibits phosphatidylinositol 3-kinase through binding to PIKE-L.Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18200-5. doi: 10.1073/pnas.0405971102. Epub 2004 Dec 14.
• [18] Expression of E-cadherin-catenin complex in human benign schwannomas.Histol Histopathol. 2002 Jan;17(1):39-44. doi: 10.14670/HH-17.39.
• [19] Schwannoma gene therapy by adeno-associated virus delivery of the pore-forming protein Gasdermin-D.Cancer Gene Ther. 2019 Sep;26(9-10):259-267. doi: 10.1038/s41417-018-0077-3. Epub 2019 Jan 9.
• [20] Functional analysis of the relationship between the neurofibromatosis 2 tumor suppressor and its binding partner, hepatocyte growth factor-regulated tyrosine kinase substrate.Hum Mol Genet. 2002 Dec 1;11(25):3167-78. doi: 10.1093/hmg/11.25.3167.
• [21] Secreted glycoprotein myocilin is a component of the myelin sheath in peripheral nerves.Glia. 2003 Aug;43(2):128-40. doi: 10.1002/glia.10233.
• [22] Global Proteome and Phospho-proteome Analysis of Merlin-deficient Meningioma and Schwannoma Identifies PDLIM2 as a Novel Therapeutic Target.EBioMedicine. 2017 Feb;16:76-86. doi: 10.1016/j.ebiom.2017.01.020. Epub 2017 Jan 18.
• [23] Universal absence of merlin, but not other ERM family members, in schwannomas.Am J Pathol. 1997 Dec;151(6):1649-54.
• [24] Duodenal Schwannoma as a Rare Association With Membranous Nephropathy: A Case Report.Am J Kidney Dis. 2019 Feb;73(2):278-280. doi: 10.1053/j.ajkd.2018.09.003. Epub 2018 Nov 16.
• [25] Transcriptional mRNA of BMP-2, 3, 4 and 5 in trigeminal nerve, benign and malignant peripheral nerve sheath tumors.Histol Histopathol. 2001 Oct;16(4):1013-9. doi: 10.14670/HH-16.1013.
• [26] 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.
• [27] Alterations in the NF2/LATS1/LATS2/YAP Pathway in Schwannomas.J Neuropathol Exp Neurol. 2015 Oct;74(10):952-9. doi: 10.1097/NEN.0000000000000238.
• [28] TP53, MSH4, and LATS1 germline mutations in a family with clustering of nervous system tumors.Am J Pathol. 2014 Sep;184(9):2374-81. doi: 10.1016/j.ajpath.2014.05.017. Epub 2014 Jul 18.
• [29] Variation in SIPA1L2 is correlated with phenotype modification in Charcot- Marie- Tooth disease type 1A.Ann Neurol. 2019 Mar;85(3):316-330. doi: 10.1002/ana.25426.
• [30] Neurofibromatosis type 2 and related disorders.Curr Opin Oncol. 2019 Nov;31(6):562-567. doi: 10.1097/CCO.0000000000000579.
• [31] Immunohistochemical Approach to the Differential Diagnosis of Meningiomas and Their Mimics.J Neuropathol Exp Neurol. 2017 Apr 1;76(4):289-298. doi: 10.1093/jnen/nlx008.