Details of Disease

General Information of Disease (ID: DIS2XXH5)

• Disease Name: Paraganglioma
• Synonyms: chemodectoma; tumour of the paraganglion; tumour of paraganglion; tumor of the paraganglion; tumor of paraganglion; paraganglion tumour; paraganglion tumor; paraganglion neoplasm; paragangliomas; paraganglioma; neoplasm of the paraganglion; neoplasm of paraganglion; Paraganglionic tumour; Paraganglionic tumor; Paraganglionic neoplasm
• Disease Class: 2E92: Digestive organ benign neoplasm
• Definition: A benign or malignant neoplasm arising from paraganglia located along the sympathetic or parasympathetic nerves. Infrequently, it may arise outside the usual distribution of the sympathetic and parasympathetic paraganglia. Tumors arising from the adrenal gland medulla are called pheochromocytomas. Morphologically, paragangliomas usually display a nesting (Zellballen) growth pattern. There are no reliable morphologic criteria to distinguish between benign and malignant paragangliomas. The only definitive indicator of malignancy is the presence of regional or distant metastases.
• Disease Hierarchy:
  DISBZDUL: Autonomic nervous system neoplasm
  DISNPLOO: Neuroendocrine neoplasm
  DIS2IQBH: Neurocristopathy
  DISD715V: Hereditary neurological disease
  DIS2XXH5: Paraganglioma
• ICD Code: ICD-11: ICD-11: 2E92.2
• Disease Identifiers:
  MONDO ID: MONDO_0000448
  MESH ID: D010235
  UMLS CUI: C0030421
  MedGen ID: 10571
  HPO ID: HP:0002668
  SNOMED CT ID: 127027008

Drug-Interaction Atlas (DIA) of This Disease

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
EO2401	DMCN3UU	Phase 1/2	Vaccine	[1]

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
BAP1	TT47RXJ	Strong	Altered Expression	[2]
CSF2RA	TT6MP2Z	Strong	Genetic Variation	[3]
EGLN1	TT9ISBX	Strong	Genetic Variation	[4]
EGLN2	TTMHFRY	Strong	Genetic Variation	[5]
EPAS1	TTWPA54	Strong	Genetic Variation	[6]
JAG2	TTOJY1B	Strong	Biomarker	[7]
PDE11A	TTTWC79	Strong	Genetic Variation	[8]
PNMT	TT0NZIC	Strong	Biomarker	[9]
PPY	TTIB95A	Strong	Altered Expression	[10]
SLC18A2	TTNZRI3	Strong	Genetic Variation	[11]
SLC26A4	TT7X02I	Strong	Genetic Variation	[12]
SLC6A2	TTAWNKZ	Strong	Altered Expression	[13]
SORD	TTLSRBZ	Strong	Genetic Variation	[14]
SST	TTWF7UG	Strong	Biomarker	[15]
SSTR2	TTZ6T9E	Strong	Biomarker	[16]
TH	TTUHP71	Strong	Biomarker	[17]
VHL	TTEMWSD	Strong	Genetic Variation	[18]

This Disease Is Related to 35 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
MDH2	OT7364GY	Limited	Genetic Variation	[19]
MEN1	OTN6U6V0	moderate	Biomarker	[20]
AIP	OTDJ3OSV	Strong	Genetic Variation	[8]
ATRX	OT77RSQW	Strong	Genetic Variation	[21]
CDC73	OT6JASZ1	Strong	Genetic Variation	[22]
CHGA	OTXYX5JH	Strong	Biomarker	[23]
CHGB	OT7SAQT2	Strong	Biomarker	[24]
CMAS	OTFQJG3C	Strong	Biomarker	[25]
CNTN4	OTULXVE0	Strong	Altered Expression	[26]
CRYGD	OTW29JC4	Strong	Biomarker	[27]
DLST	OTBDF9HJ	Strong	Genetic Variation	[28]
FH	OTEQWU6Q	Strong	Biomarker	[29]
GPR68	OT1NXSMN	Strong	Altered Expression	[30]
INSM1	OTG8RV8E	Strong	Biomarker	[31]
ISCU	OTSW6DQP	Strong	Biomarker	[32]
MAML3	OTZFV53Z	Strong	Genetic Variation	[33]
MAX	OTKZ0YKM	Strong	Genetic Variation	[34]
MPZL2	OTKFNDUI	Strong	Genetic Variation	[12]
MYO5B	OTCKL3W3	Strong	Genetic Variation	[35]
NLGN4X	OTDJGBK8	Strong	Genetic Variation	[3]
NRTN	OT4PAKUY	Strong	Biomarker	[36]
PDE8B	OT4217NK	Strong	Genetic Variation	[8]
PDP1	OT82RTMT	Strong	Biomarker	[37]
PHOX2B	OT3SFR2O	Strong	Altered Expression	[38]
PPP2R1B	OTFIHQGD	Strong	Biomarker	[39]
RASSF5	OT6Q41I2	Strong	Biomarker	[40]
SARDH	OTQ49Q27	Strong	Genetic Variation	[14]
SDHAF2	OT0UG9H5	Strong	Genetic Variation	[34]
SDHAF3	OTD2JO6B	Strong	Genetic Variation	[41]
SDHC	OTC8G2MX	Strong	Biomarker	[42]
SDS	OT5WTJ2M	Strong	Genetic Variation	[14]
SLC22A18	OT9C3KR4	Strong	Biomarker	[43]
SYP	OTFJKMO4	Strong	Biomarker	[44]
TMEM127	OTYHUXC1	Strong	Genetic Variation	[45]
TRAP1	OTNG0L8J	Strong	Biomarker	[46]

References

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• [21] Telomerase Activation and ATRX Mutations Are Independent Risk Factors for Metastatic Pheochromocytoma and Paraganglioma.Clin Cancer Res. 2019 Jan 15;25(2):760-770. doi: 10.1158/1078-0432.CCR-18-0139. Epub 2018 Oct 9.
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• [25] The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney-Stratakis syndrome): molecular genetics and clinical implications.J Intern Med. 2009 Jul;266(1):43-52. doi: 10.1111/j.1365-2796.2009.02110.x.
• [26] Expression of Contactin 4 Is Associated With Malignant Behavior in Pheochromocytomas and Paragangliomas.J Clin Endocrinol Metab. 2018 Jan 1;103(1):46-55. doi: 10.1210/jc.2017-01314.
• [27] Germline SDHB and SDHD mutations in pheochromocytoma and paraganglioma patients.Endocr Connect. 2018 Dec 1;7(12):1217-1225. doi: 10.1530/EC-18-0325.
• [28] Recurrent Germline DLST Mutations in Individuals with Multiple Pheochromocytomas and Paragangliomas.Am J Hum Genet. 2019 Apr 4;104(4):651-664. doi: 10.1016/j.ajhg.2019.02.017. Epub 2019 Mar 28.
• [29] Metabolome-guided genomics to identify pathogenic variants in isocitrate dehydrogenase, fumarate hydratase, and succinate dehydrogenase genes in pheochromocytoma and paraganglioma.Genet Med. 2019 Mar;21(3):705-717. doi: 10.1038/s41436-018-0106-5. Epub 2018 Jul 27.
• [30] Comprehensive Assessment of GPR68 Expression in Normal and Neoplastic Human Tissues Using a Novel Rabbit Monoclonal Antibody.Int J Mol Sci. 2019 Oct 23;20(21):5261. doi: 10.3390/ijms20215261.
• [31] Insulinoma-associated Protein 1 (INSM1) in Thoracic Tumors is Less Sensitive but More Specific Compared With Synaptophysin, Chromogranin A, and CD56.Appl Immunohistochem Mol Morphol. 2020 Mar;28(3):237-242. doi: 10.1097/PAI.0000000000000715.
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• [33] Master regulator analysis of paragangliomas carrying SDHx, VHL, or MAML3 genetic alterations.BMC Cancer. 2019 Jun 24;19(1):619. doi: 10.1186/s12885-019-5813-z.
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• [37] Effects of dichloroacetate as single agent or in combination with GW6471 and metformin in paraganglioma cells.Sci Rep. 2018 Sep 11;8(1):13610. doi: 10.1038/s41598-018-31797-5.
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• [39] Genomic organization and precise physical location of protein phosphatase 2A regulatory subunit A beta isoform gene on chromosome band 11q23.Gene. 1998 Sep 14;217(1-2):107-16. doi: 10.1016/s0378-1119(98)00350-3.
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• [43] Parent-of-origin tumourigenesis is mediated by an essential imprinted modifier in SDHD-linked paragangliomas: SLC22A18 and CDKN1C are candidate tumour modifiers.Hum Mol Genet. 2016 Sep 1;25(17):3715-3728. doi: 10.1093/hmg/ddw218. Epub 2016 Jul 8.
• [44] Immunohistochemical expression patterns of S100, synaptophysin, chromogranin A and neuron specific enolase in predicting malignant behaviour in paragangliomas.J BUON. 2018 Sep-Oct;23(5):1540-1545.
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