Details of Disease

General Information of Disease (ID: DIS46HZU)

• Disease Name: Malignant rhabdoid tumour
• Synonyms: rhabdoid cancer; rhabdoid tumor; rhabdoid sarcoma; malignant rhabdoid tumour; malignant rhabdoid tumor
• Disease Class: 2A00: Brain cancer
• Definition: An aggressive malignant embryonal neoplasm usually occurring during childhood. It is characterized by the presence of large cells with abundant cytoplasm, large eccentric nucleus, and a prominent nucleolus and it is associated with abnormalities of chromosome 22. It can arise from the central nervous system, kidney, and the soft tissues. The prognosis is poor.
• Disease Hierarchy:
  DIS5MQSB: Embryonal neoplasm
  DISSN8XB: Soft tissue sarcoma
  DIS46HZU: Malignant rhabdoid tumour
• ICD Code:
  ICD-11: ICD-11: 2A00.1Y
  Expand ICD-11: 'XH3RF3
• Disease Identifiers:
  MONDO ID: MONDO_0002728
  MESH ID: D018335
  UMLS CUI: C0206743
  MedGen ID: 64646
  HPO ID: HP:0034557
  Orphanet ID: 69077
  SNOMED CT ID: 1156418001

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
Tazemetostat	DMWP1BH	Approved	Small molecular drug	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
RHD	TTLCKI8	Limited	Biomarker	[2]
BRD9	TTR7L5Y	Strong	Genetic Variation	[3]
CRTC1	TT4GO0F	Strong	Biomarker	[4]
PLK4	TTGPNZQ	Strong	Biomarker	[5]
SMARCA4	TTVQEZS	Strong	Biomarker	[6]
CLDN6	TTKSV48	Definitive	Altered Expression	[7]

This Disease Is Related to 19 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
BANF1	OTP7Z38L	Limited	Genetic Variation	[8]
BCOR	OTG013AX	Limited	Genetic Variation	[9]
BIN1	OTK8O0X8	Limited	Altered Expression	[10]
CIC	OTFXCHNZ	Limited	Genetic Variation	[9]
CNN1	OTVPG39Z	Limited	Altered Expression	[11]
CROCC	OTVNOZSM	Limited	Genetic Variation	[12]
CRX	OTH435SV	Limited	Biomarker	[13]
CRYBB2	OTL0Z8E6	Limited	Genetic Variation	[14]
DMBX1	OT43YF6N	Limited	Biomarker	[13]
FXYD5	OT81DIOD	Limited	Altered Expression	[15]
MYF5	OTTVO2S5	Limited	Biomarker	[16]
NSF	OTKRJ2ZT	Limited	Altered Expression	[17]
NUTM1	OTONYC08	Limited	Altered Expression	[18]
PHF5A	OTS94JFM	Limited	Altered Expression	[19]
RSPH14	OT2OF6C3	Limited	Biomarker	[20]
PGBD5	OTP051G2	Strong	Biomarker	[21]
RPL5	OTM8EBRI	Strong	Biomarker	[22]
SMARCA1	OT0Y6PTU	Strong	Genetic Variation	[23]
STIM1	OT8CLQ1W	Strong	Biomarker	[24]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Differential expression of miRNAs in rhabdomyosarcoma and malignant rhabdoid tumor.Exp Cell Res. 2012 Dec 10;318(20):2567-77. doi: 10.1016/j.yexcr.2012.07.015. Epub 2012 Sep 18.
• [3] BRD9 defines a SWI/SNF sub-complex and constitutes a specific vulnerability in malignant rhabdoid tumors.Nat Commun. 2019 Apr 23;10(1):1881. doi: 10.1038/s41467-019-09891-7.
• [4] The TORC1/2 inhibitor TAK228 sensitizes atypical teratoid rhabdoid tumors to cisplatin-induced cytotoxicity.Neuro Oncol. 2017 Oct 1;19(10):1361-1371. doi: 10.1093/neuonc/nox067.
• [5] A functional screening of the kinome identifies the Polo-like kinase 4 as a potential therapeutic target for malignant rhabdoid tumors, and possibly, other embryonal tumors of the brain.Pediatr Blood Cancer. 2017 Nov;64(11). doi: 10.1002/pbc.26551. Epub 2017 Apr 11.
• [6] SMARCA4-deficient undifferentiated uterine sarcoma (malignant rhabdoid tumor of the uterus): a clinicopathologic entity distinct from undifferentiated carcinoma.Mod Pathol. 2018 Sep;31(9):1442-1456. doi: 10.1038/s41379-018-0049-z. Epub 2018 Apr 26.
• [7] Epithelioid versus rhabdoid glioblastomas are distinguished by monosomy 22 and immunohistochemical expression of INI-1 but not claudin 6.Am J Surg Pathol. 2010 Mar;34(3):341-54. doi: 10.1097/PAS.0b013e3181ce107b.
• [8] SMARCB1 is required for widespread BAF complex-mediated activation of enhancers and bivalent promoters.Nat Genet. 2017 Nov;49(11):1613-1623. doi: 10.1038/ng.3958. Epub 2017 Sep 25.
• [9] Review with novel markers facilitates precise categorization of 41 cases of diagnostically challenging, "undifferentiated small round cell tumors". A clinicopathologic, immunophenotypic and molecular analysis.Ann Diagn Pathol. 2018 Jun;34:1-12. doi: 10.1016/j.anndiagpath.2017.11.011. Epub 2017 Nov 29.
• [10] Epigenetic inactivation of the tumor suppressor BIN1 drives proliferation of SNF5-deficient tumors.Cell Cycle. 2012 May 15;11(10):1956-65. doi: 10.4161/cc.20280. Epub 2012 May 15.
• [11] Malignant rhabdoid-tumor cell line showing neural and smooth-muscle-cell phenotypes.Int J Cancer. 1999 Aug 27;82(5):678-86. doi: 10.1002/(sici)1097-0215(19990827)82:5<678::aid-ijc10>3.0.co;2-k.
• [12] Centrosome Linker-induced Tetraploid Segregation Errors Link Rhabdoid Phenotypes and Lethal Colorectal Cancers.Mol Cancer Res. 2018 Sep;16(9):1385-1395. doi: 10.1158/1541-7786.MCR-18-0062. Epub 2018 May 21.
• [13] CRX/OTX3: a useful marker in the differential diagnosis of tumors of the pineal region and indicator of photoreceptor differentiation in medulloblastomas and atypical teratoid rhabdoid tumors.Appl Immunohistochem Mol Morphol. 2013 May;21(3):248-53. doi: 10.1097/PAI.0b013e3182649dad.
• [14] The t(11;22)(p15.5;q11.23) in a retroperitoneal rhabdoid tumor also includes a regional deletion distal to CRYBB2 on 22q.Genes Chromosomes Cancer. 1995 Jul;13(3):145-50. doi: 10.1002/gcc.2870130302.
• [15] Prognostic significance of dysadherin expression in epithelioid sarcoma and its diagnostic utility in distinguishing epithelioid sarcoma from malignant rhabdoid tumor.Mod Pathol. 2006 Jun;19(6):820-31. doi: 10.1038/modpathol.3800599.
• [16] Expression of pericyte, mesangium and muscle markers in malignant rhabdoid tumor cell lines: differentiation-induction using 5-azacytidine.Cancer Sci. 2003 Dec;94(12):1059-65. doi: 10.1111/j.1349-7006.2003.tb01401.x.
• [17] Malignant rhabdoid tumor shows incomplete neural characteristics as revealed by expression of SNARE complex.J Neurosci Res. 2002 Sep 1;69(5):642-52. doi: 10.1002/jnr.10330.
• [18] Targeting chromatin defects in selected solid tumors based on oncogene addiction, synthetic lethality and epigenetic antagonism.Ann Oncol. 2017 Feb 1;28(2):254-269. doi: 10.1093/annonc/mdw552.
• [19] SMARCB1/INI1 protein expression in round cell soft tissue sarcomas associated with chromosomal translocations involving EWS: a special reference to SMARCB1/INI1 negative variant extraskeletal myxoid chondrosarcoma.Am J Surg Pathol. 2008 Aug;32(8):1168-74. doi: 10.1097/PAS.0b013e318161781a.
• [20] Isolation of genes from the rhabdoid tumor deletion region in chromosome band 22q11.2.Gene. 2000 Jan 4;241(1):133-41. doi: 10.1016/s0378-1119(99)00456-4.
• [21] PGBD5 promotes site-specific oncogenic mutations in human tumors.Nat Genet. 2017 Jul;49(7):1005-1014. doi: 10.1038/ng.3866. Epub 2017 May 15.
• [22] Identification of RPL5 and RPL10 as novel diagnostic biomarkers of Atypical teratoid/rhabdoid tumors.Cancer Cell Int. 2018 Nov 20;18:190. doi: 10.1186/s12935-018-0681-1. eCollection 2018.
• [23] MDM2 and MDM4 Are Therapeutic Vulnerabilities in Malignant Rhabdoid Tumors.Cancer Res. 2019 May 1;79(9):2404-2414. doi: 10.1158/0008-5472.CAN-18-3066. Epub 2019 Feb 12.
• [24] Exon structure and promoter identification of STIM1 (alias GOK), a human gene causing growth arrest of the human tumor cell lines G401 and RD.Cytogenet Cell Genet. 1999;86(3-4):214-8. doi: 10.1159/000015341.