SMARCB1 loss activates patient-specific distal oncogenic enhancers in malignant rhabdoid tumors.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 Dec 2023
01 Dec 2023
Historique:
received:
22
01
2023
accepted:
10
11
2023
medline:
4
12
2023
pubmed:
2
12
2023
entrez:
1
12
2023
Statut:
epublish
Résumé
Malignant rhabdoid tumor (MRT) is a highly malignant and often lethal childhood cancer. MRTs are genetically defined by bi-allelic inactivating mutations in SMARCB1, a member of the BRG1/BRM-associated factors (BAF) chromatin remodeling complex. Mutations in BAF complex members are common in human cancer, yet their contribution to tumorigenesis remains in many cases poorly understood. Here, we study derailed regulatory landscapes as a consequence of SMARCB1 loss in the context of MRT. Our multi-omics approach on patient-derived MRT organoids reveals a dramatic reshaping of the regulatory landscape upon SMARCB1 reconstitution. Chromosome conformation capture experiments subsequently reveal patient-specific looping of distal enhancer regions with the promoter of the MYC oncogene. This intertumoral heterogeneity in MYC enhancer utilization is also present in patient MRT tissues as shown by combined single-cell RNA-seq and ATAC-seq. We show that loss of SMARCB1 activates patient-specific epigenetic reprogramming underlying MRT tumorigenesis.
Identifiants
pubmed: 38040699
doi: 10.1038/s41467-023-43498-3
pii: 10.1038/s41467-023-43498-3
pmc: PMC10692191
doi:
Substances chimiques
SMARCB1 Protein
0
Transcription Factors
0
SMARCB1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7762Subventions
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : 850571
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : 865459
Organisme : Stichting Kinderen Kankervrij (KiKa)
ID : 338
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)
ID : 203.003
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)
ID : 181.014
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)
ID : 016.16.316
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : P2BSP3-174991
Organisme : Human Frontier Science Program (HFSP)
ID : LT000209/2018-L
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Skłodowska-Curie Actions (H2020 Excellent Science - Marie Skłodowska-Curie Actions)
ID : 798573
Informations de copyright
© 2023. The Author(s).
Références
Cancer Cell. 2002 Nov;2(5):415-25
pubmed: 12450796
Elife. 2017 Mar 13;6:
pubmed: 28287392
Cell. 2017 May 18;169(5):930-944.e22
pubmed: 28525758
Nat Rev Cancer. 2018 Jul;18(7):407-418
pubmed: 29692415
Nat Methods. 2020 Jun;17(6):615-620
pubmed: 32366989
Nat Biotechnol. 2010 May;28(5):495-501
pubmed: 20436461
Cell Stem Cell. 2017 Feb 2;20(2):191-204.e5
pubmed: 27889319
Nat Immunol. 2019 Feb;20(2):163-172
pubmed: 30643263
Bioinformatics. 2011 Jan 15;27(2):270-1
pubmed: 21081511
Nat Methods. 2021 Nov;18(11):1333-1341
pubmed: 34725479
J Med Chem. 2016 Feb 25;59(4):1425-39
pubmed: 25856009
Cell Rep. 2021 Aug 24;36(8):109568
pubmed: 34433038
Cell Rep. 2018 Apr 10;23(2):349-360
pubmed: 29641996
Cell. 2018 Nov 15;175(5):1272-1288.e20
pubmed: 30343899
Trends Cancer. 2016 May;2(5):217-218
pubmed: 28741508
Nat Cell Biol. 2018 Dec;20(12):1410-1420
pubmed: 30397315
Science. 2016 Nov 11;354(6313):769-773
pubmed: 27708057
Genome Res. 2015 Apr;25(4):504-13
pubmed: 25677180
Bioinformatics. 2014 Oct 15;30(20):2843-51
pubmed: 24974202
Genome Biol. 2009;10(3):R25
pubmed: 19261174
Nat Commun. 2020 Mar 11;11(1):1310
pubmed: 32161258
Cell. 2014 Dec 18;159(7):1665-80
pubmed: 25497547
BMC Genomics. 2013 Sep 20;14:632
pubmed: 24053356
Nucleic Acids Res. 2018 Sep 6;46(15):e91
pubmed: 29800273
Nat Commun. 2017 Mar 06;8:14648
pubmed: 28262751
Nat Commun. 2017 Aug 21;8(1):300
pubmed: 28824165
Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):333-49
pubmed: 25195934
Genome Biol. 2014;15(12):550
pubmed: 25516281
Science. 2013 Mar 29;339(6127):1546-58
pubmed: 23539594
Nat Genet. 2017 Nov;49(11):1613-1623
pubmed: 28945250
Nat Commun. 2019 Apr 23;10(1):1881
pubmed: 31015438
Genome Biol. 2019 Dec 23;20(1):296
pubmed: 31870423
Elife. 2019 Apr 29;8:
pubmed: 31033435
NAR Genom Bioinform. 2021 May 22;3(2):lqab040
pubmed: 34046591
Cell. 2021 Jun 24;184(13):3573-3587.e29
pubmed: 34062119
Nat Rev Genet. 2013 Nov;14(11):765-80
pubmed: 24105274
Cancer Discov. 2022 Feb;12(2):562-585
pubmed: 34561242
Cell. 2013 Nov 7;155(4):934-47
pubmed: 24119843
Cell Rep. 2019 Nov 19;29(8):2338-2354.e7
pubmed: 31708418
Nat Commun. 2021 Mar 3;12(1):1407
pubmed: 33658498
Cancer Metastasis Rev. 2018 Mar;37(1):173-187
pubmed: 29322354
Nat Med. 2019 May;25(5):838-849
pubmed: 31011202
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
Genes Dev. 2021 Jan 1;35(1-2):65-81
pubmed: 33334824
PLoS One. 2013;8(1):e55119
pubmed: 23355908
Trends Cancer. 2018 Dec;4(12):810-822
pubmed: 30470303
Nature. 1998 Jul 9;394(6689):203-6
pubmed: 9671307
Nature. 2009 Apr 9;458(7239):719-24
pubmed: 19360079
Nat Commun. 2021 Dec 15;12(1):7308
pubmed: 34911936
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Cancer Cell. 2019 Jan 14;35(1):95-110.e8
pubmed: 30595504
Bioinformatics. 2022 May 13;38(10):2943-2945
pubmed: 35561197
Nature. 2018 Mar 15;555(7696):321-327
pubmed: 29489754
Acta Neuropathol. 2012 Sep;124(3):439-47
pubmed: 22661320
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W187-91
pubmed: 24799436
Cancer Cell. 2020 Aug 10;38(2):212-228.e13
pubmed: 32707078
Nature. 2008 Feb 14;451(7180):796-801
pubmed: 18235444
Annu Rev Pathol. 2015;10:145-71
pubmed: 25387058
Nat Med. 2018 Oct;24(10):1611-1624
pubmed: 30150718
Cell. 2017 Aug 24;170(5):875-888.e20
pubmed: 28757253
Nat Genet. 2021 Jan;53(1):100-109
pubmed: 33318687
Genome Biol. 2013 Apr 25;14(4):R36
pubmed: 23618408
Nature. 2018 Jan 25;553(7689):515-520
pubmed: 29342133
PLoS Genet. 2021 Mar 22;17(3):e1009446
pubmed: 33750945
Nature. 2018 Apr;556(7702):457-462
pubmed: 29643510
Nat Genet. 2023 Feb;55(2):333-345
pubmed: 36539617
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Dev Biol. 2016 Mar 1;411(1):15-24
pubmed: 26806701
Genome Biol. 2015 Dec 01;16:259
pubmed: 26619908
Nat Methods. 2011 Dec 04;9(1):81-3
pubmed: 22138822
Nat Genet. 2013 Jun;45(6):592-601
pubmed: 23644491
Nat Genet. 2017 Feb;49(2):289-295
pubmed: 27941797
Nat Cancer. 2022 Aug;3(8):994-1011
pubmed: 35788723
Nat Commun. 2022 Mar 22;13(1):1544
pubmed: 35318328
Cell. 2018 May 31;173(6):1398-1412.e22
pubmed: 29731168
Cancer Cell. 2016 Dec 12;30(6):891-908
pubmed: 27960086
Genes Dev. 2018 Jan 1;32(1):42-57
pubmed: 29378788