Details of Disease

General Information of Disease (ID: DISSBE0K)

• Disease Name: Anaplastic astrocytoma
• Synonyms: grade III astrocytic tumor; anaplastic astrocytoma; grade III astrocytoma; malignant astrocytoma; astrocytoma, anaplastic, malignant; grade III astrocytic tumour; grade III astrocytic neoplasm
• Disease Class: 2A00: Brain cancer
• Definition: Anaplastic astrocytoma is a rare, high-grade, malignant glial tumor, histologically characterized by abundance of pleomorphic astrocytes and multiple mitotic figures, often associated with diffuse infiltration of the surrounding tissue, considerable edema and mass effect and involvement of the contralateral brain. Depending on the primary localization of the tumor, patients can present with signs of raised intracranial pressure (headache, vomiting, papilledema), seizures, progressive neurological deficits, and/or behavioral changes. The tumor is most commonly localized in the frontal and temporal lobes, brain stem and spinal cord.
• Disease Hierarchy:
  DISL3V18: Astrocytoma
  DIS8I7W1: Anaplastic cancer
  DISMP7I5: High grade astrocytic tumor
  DISSBE0K: Anaplastic astrocytoma
• ICD Code:
  ICD-11: ICD-11: 2A00.0
  ICD-9: ICD-9: 191
  Expand ICD-11: 'XH96C7
  Expand ICD-9: 191
• Disease Identifiers:
  MONDO ID: MONDO_0016684
  MESH ID: D001254
  UMLS CUI: C0334579
  MedGen ID: 137784
  Orphanet ID: 251589
  SNOMED CT ID: 55353007

Drug-Interaction Atlas (DIA) of This Disease

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
TG02	DMZFIGQ	Phase 1/2	Small molecular drug	[1]
PAC1	DMYQUIP	Phase 1	Small molecular drug	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 26 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ATP2A2	TTE6THL	Limited	Altered Expression	[2]
BRAF	TT0EOB8	Limited	Autosomal dominant	[3]
HIF1A	TTSN6QU	Limited	Altered Expression	[4]
MET	TTNDSF4	Limited	Biomarker	[5]
ACVR1	TTJNBQA	moderate	Biomarker	[6]
AR	TTKPW01	moderate	Biomarker	[7]
ESR1	TTZAYWL	moderate	Biomarker	[7]
ESR2	TTOM3J0	moderate	Biomarker	[7]
FGFR1	TTRLW2X	moderate	Biomarker	[8]
NCOA3	TT124R0	moderate	Biomarker	[7]
NTRK2	TTKN7QR	moderate	Biomarker	[8]
BRAF	TT0EOB8	Strong	Genetic Variation	[9]
DLL3	TT1C9K6	Strong	Biomarker	[10]
FGFR4	TT1KX2S	Strong	Genetic Variation	[11]
HGF	TT4V2JM	Strong	Biomarker	[12]
LATS2	TTML7FG	Strong	Biomarker	[13]
MGMT	TTJ8DV7	Strong	Biomarker	[14]
MMP3	TTUZ2L5	Strong	Biomarker	[15]
NOTCH1	TTB1STW	Strong	Biomarker	[10]
NOTCH2	TT82FVD	Strong	Altered Expression	[16]
PTPN11	TT7WUAV	Strong	Biomarker	[17]
RNMT	TTG45HY	Strong	Biomarker	[18]
SLC38A5	TTC8YPT	Strong	Biomarker	[19]
TMEM97	TT9NXW4	Strong	Altered Expression	[20]
TNFRSF13C	TT7NJSE	Strong	Altered Expression	[21]
METAP2	TTZL0OI	Definitive	Genetic Variation	[22]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC20A1	DTMULXV	moderate	Altered Expression	[23]

This Disease Is Related to 43 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
BRAF	OT7S81XQ	Limited	Autosomal dominant	[3]
IDH2	OTTQA4PB	Limited	Genetic Variation	[24]
APIP	OT8ZABOU	Disputed	Biomarker	[25]
ATP1B2	OTYTBYVU	Disputed	Altered Expression	[26]
ATRN	OTTCLOPV	Disputed	Biomarker	[27]
CEP85L	OTSHJFOT	Disputed	Biomarker	[25]
KIAA1549	OTA5B18F	moderate	Biomarker	[8]
KIF14	OTXHT4JM	moderate	Biomarker	[28]
NDRG1	OTVO66BO	moderate	Biomarker	[29]
NF1	OTC29NHH	moderate	Biomarker	[8]
POU1F1	OTXT8A5C	moderate	Altered Expression	[23]
ADGRE2	OTUYJVYG	Strong	Biomarker	[30]
ADGRE5	OTTSB84Q	Strong	Biomarker	[30]
APOD	OTT77XW8	Strong	Biomarker	[31]
APTX	OTPAS5G8	Strong	Biomarker	[32]
ATP23	OT303R2T	Strong	Biomarker	[33]
ATRX	OT77RSQW	Strong	Genetic Variation	[34]
CDCA7L	OT1FFWKC	Strong	Altered Expression	[35]
CYC1	OT0962IM	Strong	Altered Expression	[36]
DMBT1	OTVNU9D9	Strong	Genetic Variation	[37]
DUSP4	OT6WAO12	Strong	Posttranslational Modification	[38]
GPR162	OTK4LT3K	Strong	Genetic Variation	[39]
H3-3B	OT9XHQ3C	Strong	Genetic Variation	[40]
HEY1	OTJQL0I3	Strong	Biomarker	[10]
HEY2	OTU4J3ZI	Strong	Biomarker	[10]
KIF15	OTJRJEXL	Strong	Biomarker	[41]
KIFC1	OTNQDS00	Strong	Biomarker	[41]
LATS1	OTOOCG4R	Strong	Biomarker	[13]
LRRN2	OTGP2DCY	Strong	Altered Expression	[42]
MMP25	OT3BG37V	Strong	Altered Expression	[43]
MSH4	OTJZMG1Z	Strong	Genetic Variation	[44]
OLIG2	OTMCN6D3	Strong	Biomarker	[45]
PYGO2	OTZHB2OI	Strong	Biomarker	[46]
RASD1	OT2BAJHK	Strong	Altered Expression	[47]
SCG5	OTXSJMT1	Strong	Biomarker	[48]
SLTM	OT0VRZA6	Strong	Biomarker	[18]
TFG	OT2KJENI	Strong	Genetic Variation	[49]
TSC22D1	OTN4GFWD	Strong	Altered Expression	[50]
ABR	OTZQK8JF	Definitive	Biomarker	[51]
FABP7	OTRE2H4G	Definitive	Biomarker	[52]
LAMC1	OTIG527N	Definitive	Biomarker	[53]
SETX	OTG3JNOQ	Definitive	Biomarker	[32]
SMARCE1	OTAX4ITH	Definitive	Genetic Variation	[54]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] High ATP2A2 expression correlates with better prognosis of diffuse astrocytic tumor patients.Oncol Rep. 2017 May;37(5):2865-2874. doi: 10.3892/or.2017.5528. Epub 2017 Mar 24.
• [3] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [4] Differential expression of HIF-1 in glioblastoma multiforme and anaplastic astrocytoma.Int J Oncol. 2012 Oct;41(4):1260-70. doi: 10.3892/ijo.2012.1555. Epub 2012 Jul 16.
• [5] Comparative In Vitro Study of (11)C-Methionine and (11)C-Deuterodeprenyl Uptake in Three Human Glioma Cell Lines.Cancer Biother Radiopharm. 2017 Nov;32(9):344-350. doi: 10.1089/cbr.2017.2334.
• [6] Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma.Nat Genet. 2014 May;46(5):462-6. doi: 10.1038/ng.2950. Epub 2014 Apr 6.
• [7] Expression of estrogen receptors, androgen receptor and steroid receptor coactivator-3 is negatively correlated to the differentiation of astrocytic tumors.Cancer Epidemiol. 2014 Jun;38(3):291-7. doi: 10.1016/j.canep.2014.03.001. Epub 2014 Mar 27.
• [8] Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma.Nat Genet. 2013 Aug;45(8):927-32. doi: 10.1038/ng.2682. Epub 2013 Jun 30.
• [9] Inhibition of MEK confers hypersensitivity to X-radiation in the context of BRAF mutation in a model of childhood astrocytoma.Pediatr Blood Cancer. 2015 Oct;62(10):1768-74. doi: 10.1002/pbc.25579. Epub 2015 May 15.
• [10] Inhibition of notch signaling blocks growth of glioblastoma cell lines and tumor neurospheres.Genes Cancer. 2010 Aug;1(8):822-35. doi: 10.1177/1947601910383564.
• [11] Analysis of a single nucleotide polymorphism in codon 388 of the FGFR4 gene in malignant gliomas.Cancer Lett. 2006 Aug 8;239(2):239-45. doi: 10.1016/j.canlet.2005.08.013. Epub 2005 Sep 29.
• [12] Agonists of the retinoic acid- and retinoid X-receptors inhibit hepatocyte growth factor secretion and expression in U87 human astrocytoma cells. Brain Res Mol Brain Res. 2001 Feb 19;87(1):100-8. doi: 10.1016/s0165-3806(00)00154-1.
• [13] Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma. Neurosci Res. 2006 Dec;56(4):450-8. doi: 10.1016/j.neures.2006.09.006. Epub 2006 Oct 17.
• [14] MGMT: Immunohistochemical Detection in High-Grade Astrocytomas.J Neuropathol Exp Neurol. 2019 Jan 1;78(1):57-64. doi: 10.1093/jnen/nly110.
• [15] Glycitein inhibits glioma cell invasion through down-regulation of MMP-3 and MMP-9 gene expression.Chem Biol Interact. 2010 Apr 15;185(1):18-24. doi: 10.1016/j.cbi.2010.02.037. Epub 2010 Feb 25.
• [16] Constitutive Notch2 signaling in neural stem cells promotes tumorigenic features and astroglial lineage entry.Cell Death Dis. 2012 Jun 21;3(6):e325. doi: 10.1038/cddis.2012.65.
• [17] Occurrence of high-grade glioma in Noonan syndrome: Report of two cases.Pediatr Blood Cancer. 2019 May;66(5):e27625. doi: 10.1002/pbc.27625. Epub 2019 Jan 28.
• [18] RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas.Genome Res. 2014 Nov;24(11):1765-73. doi: 10.1101/gr.165126.113. Epub 2014 Aug 18.
• [19] Increased expression of a glutamine transporter SNAT3 is a marker of malignant gliomas. Neuroreport. 2004 Mar 22;15(4):575-8.
• [20] Sigma-2 receptor/TMEM97 agonist PB221 as an alternative drug for brain tumor.BMC Cancer. 2019 May 20;19(1):473. doi: 10.1186/s12885-019-5700-7.
• [21] Molecular characterization of a novel human brain tumor-associated gene BR-3.Anticancer Res. 2002 May-Jun;22(3):1467-74.
• [22] Diagnostic utility of IDH1- and p53-mutation analysis in secondary gliosarcoma.Clin Neuropathol. 2011 Sep-Oct;30(5):231-4. doi: 10.5414/np300375.
• [23] Gefitinib inhibits sodium phosphate co-transporter III isoform 1 in a model of human malignant glioma.Anticancer Res. 2014 Nov;34(11):6527-35.
• [24] c-Met Expression Is a Useful Marker for Prognosis Prediction in IDH-Mutant Lower-Grade Gliomas and IDH-Wildtype Glioblastomas.World Neurosurg. 2019 Jun;126:e1042-e1049. doi: 10.1016/j.wneu.2019.03.040. Epub 2019 Mar 13.
• [25] Breakpoint analysis of transcriptional and genomic profiles uncovers novel gene fusions spanning multiple human cancer types.PLoS Genet. 2013 Apr;9(4):e1003464. doi: 10.1371/journal.pgen.1003464. Epub 2013 Apr 25.
• [26] Identification of novel genes associated with astrocytoma progression using suppression subtractive hybridization and real-time reverse transcription-polymerase chain reaction.Int J Cancer. 2006 Nov 15;119(10):2330-8. doi: 10.1002/ijc.22108.
• [27] Attractin is elevated in the cerebrospinal fluid of patients with malignant astrocytoma and mediates glioma cell migration.Clin Cancer Res. 2006 Nov 1;12(21):6331-6. doi: 10.1158/1078-0432.CCR-06-1296.
• [28] Inhibition of KIF14 Suppresses Tumor Cell Growth and Promotes Apoptosis in Human Glioblastoma.Cell Physiol Biochem. 2015;37(5):1659-70. doi: 10.1159/000438532. Epub 2015 Nov 5.
• [29] Hypoxia upregulates the expression of the NDRG1 gene leading to its overexpression in various human cancers.BMC Genet. 2004 Sep 2;5:27. doi: 10.1186/1471-2156-5-27.
• [30] Proportional upregulation of CD97 isoforms in glioblastoma and glioblastoma-derived brain tumor initiating cells.PLoS One. 2015 Feb 25;10(2):e0111532. doi: 10.1371/journal.pone.0111532. eCollection 2015.
• [31] Progression-associated genes in astrocytoma identified by novel microarray gene expression data reanalysis.Methods Mol Biol. 2007;377:203-22. doi: 10.1007/978-1-59745-390-5_13.
• [32] 1p/19q codeletion and IDH1/2 mutation identified a subtype of anaplastic oligoastrocytomas with prognosis as favorable as anaplastic oligodendrogliomas.Neuro Oncol. 2013 Jun;15(6):775-82. doi: 10.1093/neuonc/not027. Epub 2013 Mar 13.
• [33] KUB3 amplification and overexpression in human gliomas.Glia. 2001 Oct;36(1):1-10. doi: 10.1002/glia.1090.
• [34] Phosphorylated Hsp27 is mutually exclusive with ATRX loss and the IDH1(R132H) mutation and may predict better prognosis among glioblastomas without the IDH1 mutation and ATRX loss.J Clin Pathol. 2018 Aug;71(8):702-707. doi: 10.1136/jclinpath-2018-205000. Epub 2018 Mar 17.
• [35] Cell division cycle associated 7 like predicts unfavorable prognosis and promotes invasion in glioma.Pathol Res Pract. 2019 Jan;215(1):50-56. doi: 10.1016/j.prp.2018.10.023. Epub 2018 Oct 24.
• [36] Selection of suitable reference genes for expression analysis in human glioma using RT-qPCR.J Neurooncol. 2015 May;123(1):35-42. doi: 10.1007/s11060-015-1772-7. Epub 2015 Apr 11.
• [37] PTEN, DMBT1, and p16 alterations in diffusely infiltrating astrocytomas.Int J Oncol. 2002 Sep;21(3):667-74.
• [38] Epigenetic downregulation of mitogen-activated protein kinase phosphatase MKP-2 relieves its growth suppressive activity in glioma cells.Cancer Res. 2010 Feb 15;70(4):1689-99. doi: 10.1158/0008-5472.CAN-09-3218. Epub 2010 Feb 2.
• [39] IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO.Acta Neuropathol. 2015 Jun;129(6):867-73. doi: 10.1007/s00401-015-1438-8. Epub 2015 May 12.
• [40] Pediatric thalamic glioma with H3F3A K27M mutation, which was detected before and after malignant transformation: a case report.Childs Nerv Syst. 2016 Dec;32(12):2433-2438. doi: 10.1007/s00381-016-3161-8. Epub 2016 Jul 8.
• [41] Expression of targeting protein for Xenopus kinesin-like protein 2 is associated with progression of human malignant astrocytoma.Brain Res. 2010 Sep 17;1352:200-7. doi: 10.1016/j.brainres.2010.06.060. Epub 2010 Jun 30.
• [42] GAC1, a new member of the leucine-rich repeat superfamily on chromosome band 1q32.1, is amplified and overexpressed in malignant gliomas.Oncogene. 1998 Jun 11;16(23):2997-3002. doi: 10.1038/sj.onc.1201828.
• [43] Human MT6-matrix metalloproteinase: identification, progelatinase A activation, and expression in brain tumors.Cancer Res. 2000 Feb 15;60(4):877-82.
• [44] 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.
• [45] Candidate genes for the progression of malignant gliomas identified by microarray analysis.Neurosurg Rev. 2008 Jan;31(1):83-9; discussion 89-90. doi: 10.1007/s10143-007-0107-3. Epub 2007 Oct 5.
• [46] Immunohistochemistry analysis of Pygo2 expression in central nervous system tumors.J Cell Commun Signal. 2019 Mar;13(1):75-84. doi: 10.1007/s12079-018-0476-0. Epub 2018 Jul 5.
• [47] Overexpression of RASD1 inhibits glioma cell migration/invasion and inactivates the AKT/mTOR signaling pathway.Sci Rep. 2017 Jun 9;7(1):3202. doi: 10.1038/s41598-017-03612-0.
• [48] Frequent epigenetic inactivation of the chaperone SGNE1/7B2 in human gliomas.Int J Cancer. 2012 Aug 1;131(3):612-22. doi: 10.1002/ijc.26416. Epub 2011 Oct 5.
• [49] Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas.J Transl Med. 2007 Dec 19;5:67. doi: 10.1186/1479-5876-5-67.
• [50] Downregulation of putative tumor suppressor gene TSC-22 in human brain tumors.J Surg Oncol. 2003 Jan;82(1):57-64. doi: 10.1002/jso.10180.
• [51] Deletion of chromosome arm 17p DNA sequences in pediatric high-grade and juvenile pilocytic astrocytomas.Genes Chromosomes Cancer. 1995 Mar;12(3):165-72. doi: 10.1002/gcc.2870120303.
• [52] Fatty acid binding protein 7 as a marker of glioma stem cells.Pathol Int. 2013 Nov;63(11):546-53. doi: 10.1111/pin.12109.
• [53] Identification of COL1A1 as an invasionrelated gene in malignant astrocytoma.Int J Oncol. 2018 Dec;53(6):2542-2554. doi: 10.3892/ijo.2018.4568. Epub 2018 Sep 21.
• [54] Anaplastic Astrocytoma in a Child With Coffin-Siris Syndrome and a Germline SMARCE1 Mutation: A Case Report.J Pediatr Hematol Oncol. 2020 Apr;42(3):e177-e180. doi: 10.1097/MPH.0000000000001361.