Details of Disease

Disease Name

Malignant peripheral nerve sheath tumor

neurofibrosarcoma; malignant neurofibroma; MPNST; malignant neoplasm of peripheral nerve sheath; malignant neurilemmoma; malignant tumor of peripheral nerve sheath; malignant peripheral nerve sheath tumor; malignant neurilemoma; malignant schwannoma; Malig. periph. nerve sheath tum.; malignant tumour of peripheral nerve sheath; malignant peripheral nerve sheath tumor (morphologic abnormality); schwannoma, malignant; neurofibrosarcoma, malignant; neurogenic sarcoma; malignant tumor of the peripheral nerve sheath; malignant peripheral nerve sheath neoplasm; malignant tumour of the peripheral nerve sheath; malignant neoplasm of the peripheral nerve sheath; malignant peripheral nerve sheath tumour (morphologic abnormality); malignant peripheral nerve sheath tumour [dup] (morphologic abnormality); malignant peripheral nerve sheath tumor [dup] (morphologic abnormality)

Definition

Malignant peripheral nerve sheath tumor (MPNST) is a rare and often aggressive soft tissue sarcoma occurring in a wide range of anatomical sites.

Disease Hierarchy

DISTWVT3: Peripheral nervous system cancer

DISFXKOV: Malignant glioma

DIS416YC: Tumor of cranial and spinal nerves

DISJYLBY: Nerve sheath neoplasm

DISXXOJ3: Central nervous system sarcoma

DIS0JTN6: Malignant peripheral nerve sheath tumor

Disease Identifiers

MONDO ID

MONDO_0017827

MESH ID

D018319

UMLS CUI

C0751690

MedGen ID

155614

Orphanet ID

3148

SNOMED CT ID

19897006

General Information of Disease (ID: DIS0JTN6)

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
Imatinib	DM7RJXL	Approved	Small molecular drug	[1]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 28 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
HTRA1	TT8POQR	Limited	FusionGene	[2]
BCAT1	TTES57P	Strong	Biomarker	[3]
CNP	TT71P0H	Strong	Altered Expression	[4]
CXXC5	TTVS4C3	Strong	Biomarker	[5]
DDX5	TTZKPVC	Strong	Genetic Variation	[6]
DUSP5	TTZN92A	Strong	Altered Expression	[7]
EED	TTFNJ4R	Strong	Biomarker	[8]
EZH1	TTNJA0C	Strong	Biomarker	[9]
FGF8	TTIUF3J	Strong	Genetic Variation	[10]
HDAC8	TTT6LFV	Strong	Biomarker	[11]
HDGF	TTKGV26	Strong	Biomarker	[12]
IGFBP6	TTLAYV8	Strong	Altered Expression	[13]
IL13RA2	TTMPZ7V	Strong	Altered Expression	[14]
ITGB8	TTIF29E	Strong	Biomarker	[15]
KPNB1	TTHOJ5F	Strong	Biomarker	[16]
MAGEA4	TT9EQUY	Strong	Biomarker	[17]
MAP2K7	TT6QY3J	Strong	Biomarker	[18]
MDM2	TT9TE0O	Strong	Biomarker	[19]
MSI2	TTTXQF6	Strong	Biomarker	[20]
NES	TTHZ752	Strong	Biomarker	[21]
NRAS	TTW2R9X	Strong	Biomarker	[22]
PARP2	TTQ4V96	Strong	Altered Expression	[23]
QPCT	TTJ7YTV	Strong	Genetic Variation	[24]
S100B	TTQ0V86	Strong	Biomarker	[25]
BMP2	TTP3IGX	Definitive	Altered Expression	[26]
CD38	TTPURFN	Definitive	Genetic Variation	[27]
NRG1	TTEH395	Definitive	Biomarker	[28]
TOP2A	TTCGY2K	Definitive	Biomarker	[29]
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⏷ Show the Full List of 28 DTT(s)

This Disease Is Related to 47 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
SH3PXD2A	OTYRQJIH	Limited	FusionGene	[2]
ADAP2	OTGQ8UH7	Strong	Biomarker	[30]
ATAD5	OTI8ABKF	Strong	Biomarker	[30]
CCN5	OTADU8JJ	Strong	Altered Expression	[31]
CHD4	OTBDEHDP	Strong	Biomarker	[25]
CHSY1	OTB1XSSF	Strong	Altered Expression	[32]
COIL	OTP4I4DL	Strong	Altered Expression	[33]
COPRS	OTZO53O0	Strong	Biomarker	[30]
CRABP2	OTY01V9G	Strong	Posttranslational Modification	[34]
CUL1	OTXPE1UZ	Strong	Genetic Variation	[35]
DACH1	OTMKNAGG	Strong	Biomarker	[36]
DMP1	OTBWBWW7	Strong	Altered Expression	[37]
DROSHA	OTCE68KZ	Strong	Genetic Variation	[6]
EFNA3	OTJGOUMZ	Strong	Biomarker	[38]
EIF4A1	OTMTBX6N	Strong	Biomarker	[39]
EIF4A2	OT08H03R	Strong	Biomarker	[39]
EIF4G1	OT2CF1E6	Strong	Altered Expression	[39]
EVI2A	OTR8RUXQ	Strong	Biomarker	[30]
EXOC3	OT8N3306	Strong	Biomarker	[40]
EXOC4	OT5EWXAN	Strong	Biomarker	[40]
EYA4	OTINGR3Z	Strong	Biomarker	[36]
FABP7	OTRE2H4G	Strong	Biomarker	[41]
IRX2	OTBHXXQ2	Strong	Biomarker	[42]
KANK1	OT2E7A6W	Strong	Biomarker	[5]
KDM2B	OTDMCVW7	Strong	Genetic Variation	[43]
LATS1	OTOOCG4R	Strong	Biomarker	[44]
MAGEB2	OTAGUVU5	Strong	Altered Expression	[45]
MEIS1	OTH9DKAD	Strong	Biomarker	[46]
NF1	OTC29NHH	Strong	Biomarker	[20]
NKD2	OTCYT3I6	Strong	Biomarker	[42]
NMS	OTFYS4LO	Strong	Biomarker	[47]
OMG	OTXA5C6L	Strong	Biomarker	[30]
PDGFRL	OTJPRECT	Strong	Genetic Variation	[15]
RNF135	OT18NH5N	Strong	Altered Expression	[30]
RSPO2	OT3HHXU0	Strong	Altered Expression	[48]
S100A1	OT1F2G4J	Strong	Biomarker	[25]
SMARCB1	OT2LP7LJ	Strong	Biomarker	[49]
SOX10	OTF25ULQ	Strong	Altered Expression	[50]
SPTBN2	OTDMJ75N	Strong	Altered Expression	[51]
SSX2	OT2Z6RLL	Strong	Genetic Variation	[52]
SULT4A1	OT7AL3KJ	Strong	Biomarker	[53]
SUZ12	OT655XF8	Strong	Genetic Variation	[54]
SYN1	OTMNPWC1	Strong	Biomarker	[55]
TCL1B	OT4CSO39	Strong	Biomarker	[55]
TLE1	OT50MRZ1	Strong	Altered Expression	[56]
TRIO	OT71X1AK	Strong	Altered Expression	[42]
TSHZ1	OTYQ9ECW	Strong	Genetic Variation	[24]
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⏷ Show the Full List of 47 DOT(s)

References

1	Imatinib FDA Label
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3	BCAT1 and miR-2504: novel methylome signature distinguishes spindle/desmoplastic melanoma from superficial malignant peripheral nerve sheath tumor.Mod Pathol. 2019 Mar;32(3):338-345. doi: 10.1038/s41379-018-0146-z. Epub 2018 Oct 11.
4	Ras-driven transcriptome analysis identifies aurora kinase A as a potential malignant peripheral nerve sheath tumor therapeutic target.Clin Cancer Res. 2012 Sep 15;18(18):5020-30. doi: 10.1158/1078-0432.CCR-12-1072. Epub 2012 Jul 18.
5	KANK1 inhibits cell growth by inducing apoptosis through regulating CXXC5 in human malignant peripheral nerve sheath tumors.Sci Rep. 2017 Jan 9;7:40325. doi: 10.1038/srep40325.
6	Common genetic variants in the microRNA biogenesis pathway are associated with malignant peripheral nerve sheath tumor risk in a Chinese population.Cancer Epidemiol. 2013 Dec;37(6):913-6. doi: 10.1016/j.canep.2013.05.003. Epub 2013 Jun 12.
7	Targeted Inhibition of the Dual Specificity Phosphatases DUSP1 and DUSP6 Suppress MPNST Growth via JNK.Clin Cancer Res. 2019 Jul 1;25(13):4117-4127. doi: 10.1158/1078-0432.CCR-18-3224. Epub 2019 Apr 1.
8	H3K27me3 deficiency defines a subset of dedifferentiated chondrosarcomas with characteristic clinicopathological features.Mod Pathol. 2019 Mar;32(3):435-445. doi: 10.1038/s41379-018-0140-5. Epub 2018 Oct 5.
9	EZH1/2 function mostly within canonical PRC2 and exhibit proliferation-dependent redundancy that shapes mutational signatures in cancer.Proc Natl Acad Sci U S A. 2019 Mar 26;116(13):6075-6080. doi: 10.1073/pnas.1814634116. Epub 2019 Mar 13.
10	Highly aneuploid zebrafish malignant peripheral nerve sheath tumors have genetic alterations similar to human cancers.Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16940-5. doi: 10.1073/pnas.1011548107. Epub 2010 Sep 13.
11	Evaluating the Effect of HDAC8 Inhibition in Malignant Peripheral Nerve Sheath Tumors.Methods Mol Biol. 2017;1510:365-374. doi: 10.1007/978-1-4939-6527-4_27.
12	Overexpression of Midkine in malignant peripheral nerve sheath tumor cells inhibits apoptosis and increases angiogenic potency.Int J Oncol. 2005 Nov;27(5):1433-40.
13	cDNA microarray analysis of cancer associated gene expression profiles in malignant peripheral nerve sheath tumours.J Clin Pathol. 2006 Feb;59(2):160-5. doi: 10.1136/jcp.2004.023598.
14	Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors.PLoS One. 2018 Jan 5;13(1):e0181529. doi: 10.1371/journal.pone.0181529. eCollection 2018.
15	Microarray-based copy number analysis of neurofibromatosis type-1 (NF1)-associated malignant peripheral nerve sheath tumors reveals a role for Rho-GTPase pathway genes in NF1 tumorigenesis.Hum Mutat. 2012 Apr;33(4):763-76. doi: 10.1002/humu.22044. Epub 2012 Mar 5.
16	Antitumor effects of pharmacological EZH2 inhibition on malignant peripheral nerve sheath tumor through the miR-30a and KPNB1 pathway.Mol Cancer. 2015 Mar 7;14:55. doi: 10.1186/s12943-015-0325-1.
17	MAGEA4 expression in bone and soft tissue tumors: its utility as a target for immunotherapy and diagnostic marker combined with NY-ESO-1.Virchows Arch. 2017 Sep;471(3):383-392. doi: 10.1007/s00428-017-2206-z. Epub 2017 Jul 26.
18	Genomic Status of MET Potentiates Sensitivity to MET and MEK Inhibition in NF1-Related Malignant Peripheral Nerve Sheath Tumors.Cancer Res. 2018 Jul 1;78(13):3672-3687. doi: 10.1158/0008-5472.CAN-17-3167. Epub 2018 May 2.
19	Extraskeletal osteosarcoma: MDM2 and H3K27me3 analysis of 19 cases suggest disease heterogeneity.Histopathology. 2018 Jul;73(1):147-156. doi: 10.1111/his.13506. Epub 2018 Apr 19.
20	Knockdown of HMGA2 regulates the level of autophagy via interactions between MSI2 and Beclin1 to inhibit NF1-associated malignant peripheral nerve sheath tumour growth.J Exp Clin Cancer Res. 2019 May 3;38(1):185. doi: 10.1186/s13046-019-1183-2.
21	Nestin expression as a new marker in malignant peripheral nerve sheath tumors.Pathol Int. 2007 Feb;57(2):60-7. doi: 10.1111/j.1440-1827.2006.02059.x.
22	Classic Ras Proteins Promote Proliferation and Survival via Distinct Phosphoproteome Alterations in Neurofibromin-Null Malignant Peripheral Nerve Sheath Tumor Cells.J Neuropathol Exp Neurol. 2015 Jun;74(6):568-86. doi: 10.1097/NEN.0000000000000201.
23	Poly (ADP) ribose polymerase inhibition: A potential treatment of malignant peripheral nerve sheath tumor.Cancer Biol Ther. 2016;17(2):129-38. doi: 10.1080/15384047.2015.1108486. Epub 2015 Dec 9.
24	Mxi1 mutations in human neurofibrosarcomas.Jpn J Cancer Res. 1999 Jul;90(7):740-6. doi: 10.1111/j.1349-7006.1999.tb00809.x.
25	CHD4 as a Potential Biomarker in Differentiating Between Cellular Schwannoma and Malignant Peripheral Nerve Sheath Tumor.Appl Immunohistochem Mol Morphol. 2018 Nov/Dec;26(10):775-780. doi: 10.1097/PAI.0000000000000522.
26	Combinatorial therapeutic targeting of BMP2 and MEK-ERK pathways in NF1-associated malignant peripheral nerve sheath tumors.Oncotarget. 2016 Aug 30;7(35):57171-57185. doi: 10.18632/oncotarget.11036.
27	Peripheral nerve sheath tumors from patients with neurofibromatosis type 1 do not have the chromosomal translocation t(X;18).Pediatr Dev Pathol. 2002 Mar-Apr;5(2):165-9. doi: 10.1007/s10024001-0126-y.
28	The Challenge of Cancer Genomics in Rare Nervous System Neoplasms: Malignant Peripheral Nerve Sheath Tumors as a Paradigm for Cross-Species Comparative Oncogenomics.Am J Pathol. 2016 Mar;186(3):464-77. doi: 10.1016/j.ajpath.2015.10.023. Epub 2015 Dec 28.
29	Expression and inhibition of BRD4, EZH2 and TOP2A in neurofibromas and malignant peripheral nerve sheath tumors.PLoS One. 2017 Aug 15;12(8):e0183155. doi: 10.1371/journal.pone.0183155. eCollection 2017.
30	Identification of genes potentially involved in the increased risk of malignancy in NF1-microdeleted patients.Mol Med. 2011 Jan-Feb;17(1-2):79-87. doi: 10.2119/molmed.2010.00079. Epub 2010 Sep 10.
31	Differential expression of CCN1/CYR61, CCN3/NOV, CCN4/WISP1, and CCN5/WISP2 in neurofibromatosis type 1 tumorigenesis.J Neuropathol Exp Neurol. 2010 Jan;69(1):60-9. doi: 10.1097/NEN.0b013e3181c79bff.
32	Chondroitin sulfate synthase 1 expression is associated with malignant potential of soft tissue sarcomas with myxoid substance.Hum Pathol. 2016 Apr;50:15-23. doi: 10.1016/j.humpath.2015.11.005. Epub 2015 Nov 22.
33	Expression of ALK1 and p80 in inflammatory myofibroblastic tumor and its mesenchymal mimics: a study of 135 cases.Mod Pathol. 2002 Sep;15(9):931-8. doi: 10.1097/01.MP.0000026615.04130.1F.
34	MEK inhibitors enhance therapeutic response towards ATRA in NF1 associated malignant peripheral nerve sheath tumors (MPNST) in-vitro.PLoS One. 2017 Nov 13;12(11):e0187700. doi: 10.1371/journal.pone.0187700. eCollection 2017.
35	Genome-wide high-resolution analysis of DNA copy number alterations in NF1-associated malignant peripheral nerve sheath tumors using 32K BAC array.Genes Chromosomes Cancer. 2009 Oct;48(10):897-907. doi: 10.1002/gcc.20695.
36	Inhibition of Eyes Absent Homolog 4 expression induces malignant peripheral nerve sheath tumor necrosis.Oncogene. 2010 Jan 21;29(3):368-79. doi: 10.1038/onc.2009.360. Epub 2009 Nov 9.
37	Expression of dentin matrix protein 1 in tumors causing oncogenic osteomalacia.Mod Pathol. 2004 May;17(5):573-8. doi: 10.1038/modpathol.3800084.
38	Dissecting the roles of Ephrin-A3 in malignant peripheral nerve sheath tumor by TALENs.Oncol Rep. 2015 Jul;34(1):391-8. doi: 10.3892/or.2015.3966. Epub 2015 May 8.
39	Targeting Protein Translation by Rocaglamide and Didesmethylrocaglamide to Treat MPNST and Other Sarcomas.Mol Cancer Ther. 2020 Mar;19(3):731-741. doi: 10.1158/1535-7163.MCT-19-0809. Epub 2019 Dec 17.
40	Sec6/8 regulates Bcl-2 and Mcl-1, but not Bcl-xl, in malignant peripheral nerve sheath tumor cells.Apoptosis. 2016 May;21(5):594-608. doi: 10.1007/s10495-016-1230-9.
41	Brain lipid binding protein in axon-Schwann cell interactions and peripheral nerve tumorigenesis.Mol Cell Biol. 2003 Mar;23(6):2213-24. doi: 10.1128/MCB.23.6.2213-2224.2003.
42	Frequent amplifications and abundant expression of TRIO, NKD2, and IRX2 in soft tissue sarcomas.Genes Chromosomes Cancer. 2006 Sep;45(9):829-38. doi: 10.1002/gcc.20343.
43	Confirmation of mutation landscape of NF1-associated malignant peripheral nerve sheath tumors.Genes Chromosomes Cancer. 2017 May;56(5):421-426. doi: 10.1002/gcc.22446. Epub 2017 Mar 7.
44	Programming of Schwann Cells by Lats1/2-TAZ/YAP Signaling Drives Malignant Peripheral Nerve Sheath Tumorigenesis.Cancer Cell. 2018 Feb 12;33(2):292-308.e7. doi: 10.1016/j.ccell.2018.01.005.
45	Aberrant demethylation and expression of MAGEB2 in a subset of malignant peripheral nerve sheath tumors from neurofibromatosis type 1.J Dermatol Sci. 2016 Feb;81(2):118-23. doi: 10.1016/j.jdermsci.2015.11.004. Epub 2015 Nov 28.
46	An ShRNA Screen Identifies MEIS1 as a Driver of Malignant Peripheral Nerve Sheath Tumors.EBioMedicine. 2016 Jul;9:110-119. doi: 10.1016/j.ebiom.2016.06.007. Epub 2016 Jun 4.
47	Characterization and chemosensitivity of two human malignant peripheral nerve sheath tumour cell lines derived from a patient with neurofibromatosis type 1.Virchows Arch. 1998 Nov;433(5):435-41. doi: 10.1007/s004280050271.
48	Canonical Wnt/-catenin signaling drives human schwann cell transformation, progression, and tumor maintenance.Cancer Discov. 2013 Jun;3(6):674-89. doi: 10.1158/2159-8290.CD-13-0081. Epub 2013 Mar 27.
49	Recurrent SMARCB1 Inactivation in Epithelioid Malignant Peripheral Nerve Sheath Tumors.Am J Surg Pathol. 2019 Jun;43(6):835-843. doi: 10.1097/PAS.0000000000001242.
50	Overexpression of PDGFRA cooperates with loss of NF1 and p53 to accelerate the molecular pathogenesis of malignant peripheral nerve sheath tumors.Oncogene. 2017 Feb 23;36(8):1058-1068. doi: 10.1038/onc.2016.269. Epub 2016 Aug 1.
51	Whole Exome Sequencing Reveals the Order of Genetic Changes during Malignant Transformation and Metastasis in a Single Patient with NF1-plexiform Neurofibroma.Clin Cancer Res. 2015 Sep 15;21(18):4201-11. doi: 10.1158/1078-0432.CCR-14-3049. Epub 2015 Apr 29.
52	Lack of SYT-SSX fusion transcripts in malignant peripheral nerve sheath tumors on RT-PCR analysis of 34 archival cases.Lab Invest. 2002 May;82(5):609-18. doi: 10.1038/labinvest.3780455.
53	Neurofibromatosis-associated nerve sheath tumors. Case report and review of the literature.Neurosurg Focus. 2006 Jan 15;20(1):E1. doi: 10.3171/foc.2006.20.1.2.
54	Low mutation burden and frequent loss of CDKN2A/B and SMARCA2, but not PRC2, define premalignant neurofibromatosis type 1-associated atypical neurofibromas.Neuro Oncol. 2019 Aug 5;21(8):981-992. doi: 10.1093/neuonc/noz028.
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56	Diagnostic utility of SOX10 to distinguish malignant peripheral nerve sheath tumor from synovial sarcoma, including intraneural synovial sarcoma.Mod Pathol. 2014 Jan;27(1):55-61. doi: 10.1038/modpathol.2013.115. Epub 2013 Aug 9.