EZHIP: a new piece of the puzzle towards understanding pediatric posterior fossa ependymoma.
DMG
EZHIP
H3K27M
H3K27me3
PFA ependymoma
PRC2
Journal
Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
09
09
2021
accepted:
30
10
2021
revised:
29
10
2021
pubmed:
12
11
2021
medline:
8
3
2022
entrez:
11
11
2021
Statut:
ppublish
Résumé
Ependymomas (EPN) are tumors of the central nervous system (CNS) that can arise in the supratentorial brain (ST-EPN), hindbrain or posterior fossa (PF-EPN) or anywhere in the spinal cord (SP-EPN), both in children and adults. Molecular profiling studies have identified distinct groups and subtypes in each of these anatomical compartments. In this review, we give an overview on recent findings and new insights what is driving PFA ependymomas, which is the most common group. PFA ependymomas are characterized by a young median age at diagnosis, an overall balanced genome and a bad clinical outcome (56% 10-year overall survival). Sequencing studies revealed no fusion genes or other highly recurrently mutated genes, suggesting that the disease is epigenetically driven. Indeed, recent findings have shown that the characteristic global loss of the repressive histone 3 lysine 27 trimethylation (H3K27me3) mark in PFA ependymoma is caused by aberrant expression of the enhancer of zeste homolog inhibitory protein (EZHIP) or in rare cases by H3K27M mutations, which both inhibit EZH2 thereby preventing the polycomb repressive complex 2 (PRC2) from spreading H3K27me3. We present the current status of the ongoing work on EZHIP and its essential role in the epigenetic disturbance of PFA biology. Comparisons to the oncohistone H3K27M and its role in diffuse midline glioma (DMG) are drawn, highlighting similarities but also differences between the tumor entities and underlying mechanisms. A strong focus is to point out missing information and to present directions of further research that may result in new and improved therapies for PFA ependymoma patients.
Identifiants
pubmed: 34762160
doi: 10.1007/s00401-021-02382-4
pii: 10.1007/s00401-021-02382-4
pmc: PMC8732814
doi:
Substances chimiques
EZHIP protein, human
0
Oncogene Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-13Informations de copyright
© 2021. The Author(s).
Références
Mol Cancer Res. 2009 Jun;7(6):765-86
pubmed: 19531565
Cancer Cell. 2012 Oct 16;22(4):425-37
pubmed: 23079654
Clin Cancer Res. 2012 Apr 1;18(7):2001-11
pubmed: 22338015
J Clin Oncol. 2006 Jan 10;24(2):268-73
pubmed: 16330673
Trends Cancer. 2020 Feb;6(2):147-159
pubmed: 32061304
Nat Med. 2012 Feb 06;18(2):298-301
pubmed: 22237151
Acta Neuropathol. 2019 Dec;138(6):1075-1089
pubmed: 31414211
J Neuropathol Exp Neurol. 2019 Sep 1;78(9):791-797
pubmed: 31373367
Acta Neuropathol. 2018 Aug;136(2):227-237
pubmed: 30019219
Brain Tumor Pathol. 2021 Jan;38(1):30-40
pubmed: 33130928
Nature. 2019 Aug;572(7767):67-73
pubmed: 31043743
Neoplasia. 2020 Sep;22(9):431-440
pubmed: 32652442
Genes Dev. 2013 May 1;27(9):985-90
pubmed: 23603901
Neuro Oncol. 2014 Oct;16 Suppl 4:iv1-63
pubmed: 25304271
Nat Genet. 2014 May;46(5):457-461
pubmed: 24705252
Neuro Oncol. 2019 Feb 14;21(2):189-200
pubmed: 30184215
J Neurooncol. 2014 Apr;117(2):359-64
pubmed: 24532240
Sci Rep. 2019 Feb 13;9(1):1903
pubmed: 30760837
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
Dev Growth Differ. 2004 Oct;46(5):459-70
pubmed: 15606491
Cell. 2020 Jun 11;181(6):1329-1345.e24
pubmed: 32445698
Cancer Res. 2013 Oct 15;73(20):6219-29
pubmed: 23970477
Sci Transl Med. 2016 Nov 23;8(366):366ra161
pubmed: 27881822
Acta Neuropathol. 2019 Apr;137(4):637-655
pubmed: 30770999
Int J Cancer. 2014 Mar 1;134(5):1112-22
pubmed: 23959973
Genes Cells. 2019 Oct;24(10):650-666
pubmed: 31442350
Nat Genet. 2014 May;46(5):444-450
pubmed: 24705251
Nat Med. 2017 Apr;23(4):493-500
pubmed: 28263307
Science. 2013 May 17;340(6134):857-61
pubmed: 23539183
J Neurooncol. 2016 Apr;127(2):271-8
pubmed: 26725097
Cancer Cell. 2021 Mar 8;39(3):407-422.e13
pubmed: 33545065
Curr Oncol Rep. 2020 Feb 6;22(2):19
pubmed: 32030483
Acta Neuropathol. 2020 Jun;139(6):1109-1113
pubmed: 32193787
Neuro Oncol. 2020 Dec 18;22(12):1840-1850
pubmed: 32347934
Neuro Oncol. 2018 Jan 10;20(1):123-131
pubmed: 29016894
J Hematol Oncol. 2018 Jan 15;11(1):9
pubmed: 29335012
J Clin Oncol. 2010 Jul 1;28(19):3182-90
pubmed: 20516456
Nature. 2014 Feb 27;506(7489):445-50
pubmed: 24553142
J Hematol Oncol. 2020 Jul 28;13(1):104
pubmed: 32723346
Cancer Cell. 2020 Dec 14;38(6):844-856.e7
pubmed: 33186520
Genes Dev. 2020 Aug 1;34(15-16):1051-1064
pubmed: 32675324
Nature. 2007 Aug 2;448(7153):553-60
pubmed: 17603471
Neuropathol Appl Neurobiol. 2020 Feb;46(1):73-85
pubmed: 31859390
Int J Biol Sci. 2017 May 16;13(5):652-659
pubmed: 28539837
Cancer Cell. 2017 Oct 9;32(4):520-537.e5
pubmed: 28966033
Nature. 2002 Oct 10;419(6907):624-9
pubmed: 12374981
Nature. 2010 Jul 29;466(7306):632-6
pubmed: 20639864
Acta Neuropathol. 2018 Aug;136(2):211-226
pubmed: 29909548
Cell. 2006 Apr 21;125(2):315-26
pubmed: 16630819
J Clin Oncol. 2011 Oct 20;29(30):3999-4006
pubmed: 21931021
Pharmacol Res. 2021 Sep;171:105780
pubmed: 34302977
Dev Dyn. 2005 Nov;234(3):772-82
pubmed: 16193498
Mol Cell. 2020 Nov 19;80(4):726-735.e7
pubmed: 33049227
Cancer Discov. 2021 Sep;11(9):2200-2215
pubmed: 33741710
Nat Genet. 2012 Jan 29;44(3):251-3
pubmed: 22286216
Cancer Cell. 2015 May 11;27(5):728-43
pubmed: 25965575
Nat Rev Clin Oncol. 2015 Jan;12(1):27-41
pubmed: 25286972
Oncotarget. 2018 Dec 14;9(98):37080-37096
pubmed: 30647846
Nat Commun. 2016 Apr 28;7:11316
pubmed: 27121947
Nature. 2014 Feb 27;506(7489):451-5
pubmed: 24553141
JCI Insight. 2016 Jul 7;1(10):e86837
pubmed: 27699219
Mol Cancer Res. 2017 Sep;15(9):1243-1254
pubmed: 28522693
Oncol Rep. 2014 Aug;32(2):483-90
pubmed: 24939246
Cancer. 2019 Jun 1;125(11):1867-1876
pubmed: 30768777
Nat Commun. 2019 Aug 26;10(1):3858
pubmed: 31451685
Neuro Oncol. 2021 Aug 2;23(8):1360-1370
pubmed: 33580238
Acta Neuropathol Commun. 2016 Aug 22;4(1):88
pubmed: 27550150
Nat Commun. 2019 Mar 19;10(1):1262
pubmed: 30890717
Science. 2014 Dec 19;346(6216):1529-33
pubmed: 25525250
Acta Neuropathol Commun. 2020 Nov 5;8(1):183
pubmed: 33153494
Sci Adv. 2019 Jul 03;5(7):eaax2887
pubmed: 31281901
Cancer Cell. 2013 Nov 11;24(5):660-72
pubmed: 24183680
Lancet Oncol. 2014 Jan;15(1):35-47
pubmed: 24314616
Childs Nerv Syst. 2017 Jul;33(7):1047-1051
pubmed: 28623522
Mol Cell. 2017 Dec 7;68(5):872-884.e6
pubmed: 29153392
Acta Neuropathol. 2012 Sep;124(3):439-47
pubmed: 22661320
Neuro Oncol. 2021 Aug 2;23(8):1231-1251
pubmed: 34185076
Nat Med. 2017 Apr;23(4):483-492
pubmed: 28263309
Acta Neuropathol Commun. 2020 Mar 20;8(1):37
pubmed: 32197665
Neuro Oncol. 2016 Jul;18(7):902-13
pubmed: 27022130
Childs Nerv Syst. 2009 Nov;25(11):1383-4; author reply 1385
pubmed: 19562351
Neuro Oncol. 2019 Jul 11;21(7):878-889
pubmed: 30923826
Cancer Cell. 2011 Aug 16;20(2):143-57
pubmed: 21840481
Cancer Discov. 2021 Sep;11(9):2230-2247
pubmed: 33879448
Brain Pathol. 2013 Sep;23(5):558-64
pubmed: 23414300
J Exp Med. 2019 Apr 1;216(4):966-981
pubmed: 30890554
Cancer Cell. 2020 Jul 13;38(1):44-59.e9
pubmed: 32663469
Nat Commun. 2019 May 13;10(1):2146
pubmed: 31086175
Cancer Invest. 2002;20(3):362-72
pubmed: 12025232