Bcl11b
PiggyBac
cancer evolution
genetic screening
genomics
leukemia
lymphoma
mouse
non-coding genome
quasi-insufficiency
Journal
Cell genomics
ISSN: 2666-979X
Titre abrégé: Cell Genom
Pays: United States
ID NLM: 9918284260106676
Informations de publication
Date de publication:
08 Mar 2023
08 Mar 2023
Historique:
received:
10
03
2022
revised:
05
09
2022
accepted:
08
02
2023
entrez:
23
3
2023
pubmed:
24
3
2023
medline:
24
3
2023
Statut:
epublish
Résumé
In contrast to mono- or biallelic loss of tumor-suppressor function, effects of discrete gene dysregulations, as caused by non-coding (epi)genome alterations, are poorly understood. Here, by perturbing the regulatory genome in mice, we uncover pervasive roles of subtle gene expression variation in cancer evolution. Genome-wide screens characterizing 1,450 tumors revealed that such quasi-insufficiency is extensive across entities and displays diverse context dependencies, such as distinct cell-of-origin associations in T-ALL subtypes. We compile catalogs of non-coding regions linked to quasi-insufficiency, show their enrichment with human cancer risk variants, and provide functional insights by engineering regulatory alterations in mice. As such, kilo-/megabase deletions in a
Identifiants
pubmed: 36950387
doi: 10.1016/j.xgen.2023.100276
pii: S2666-979X(23)00036-8
pmc: PMC10025556
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100276Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
Références
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nat Genet. 2017 Aug;49(8):1211-1218
pubmed: 28671688
Nature. 2020 Feb;578(7793):82-93
pubmed: 32025007
Proc Natl Acad Sci U S A. 1971 Apr;68(4):820-3
pubmed: 5279523
Nat Cell Biol. 2007 May;9(5):493-505
pubmed: 17450133
Blood. 2021 Feb 11;137(6):801-811
pubmed: 32812017
Sci Rep. 2019 Sep 20;9(1):13613
pubmed: 31541121
Nature. 2010 Nov 25;468(7323):572-5
pubmed: 21107428
PLoS Comput Biol. 2006 Dec 8;2(12):e166
pubmed: 17154714
Mol Cell. 2013 Aug 8;51(3):310-25
pubmed: 23932714
Nature. 1992 Mar 19;356(6366):215-21
pubmed: 1552940
Sci Rep. 2017 Mar 07;7:43345
pubmed: 28266526
Cell. 2016 May 19;165(5):1120-1133
pubmed: 27156451
Nature. 2013 Jul 11;499(7457):214-218
pubmed: 23770567
Blood. 2013 Aug 8;122(6):902-11
pubmed: 23741008
Cancer Cell. 2018 Feb 12;33(2):274-291.e8
pubmed: 29438697
Nat Genet. 2016 Dec;48(12):1481-1489
pubmed: 27776115
Nat Protoc. 2022 Sep;17(9):1903-1925
pubmed: 35840661
J Exp Med. 1997 Apr 21;185(8):1467-79
pubmed: 9126927
Blood. 2017 Jun 15;129(24):3264-3268
pubmed: 28408461
Oncogene. 2014 Jan 23;33(4):403-10
pubmed: 23435431
Nat Immunol. 2013 Jul;14(7):756-63
pubmed: 23708252
PLoS Comput Biol. 2013;9(8):e1003118
pubmed: 23950696
Nature. 2010 Nov 25;468(7323):567-71
pubmed: 21107427
Nat Commun. 2019 Sep 6;10(1):4059
pubmed: 31492853
Haematologica. 2014 Jan;99(1):94-102
pubmed: 23975177
Nat Commun. 2019 Mar 29;10(1):1415
pubmed: 30926791
Nature. 2011 Aug 10;476(7359):163-9
pubmed: 21833082
Nat Genet. 2015 Jan;47(1):47-56
pubmed: 25485836
Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18261-6
pubmed: 17114293
Genome Res. 2015 Apr;25(4):504-13
pubmed: 25677180
Cancer Res. 2007 Feb 15;67(4):1461-71
pubmed: 17308084
Cell. 2015 May 21;161(5):1202-1214
pubmed: 26000488
Nat Genet. 2007 May;39(5):593-5
pubmed: 17435759
Nat Cell Biol. 2018 Dec;20(12):1410-1420
pubmed: 30397315
Leuk Lymphoma. 2017 Dec;58(12):2895-2904
pubmed: 28482719
Mol Cell. 2017 Sep 21;67(6):1049-1058.e6
pubmed: 28938092
Hemasphere. 2018 May 11;2(3):e43
pubmed: 31723771
Cell. 2018 Apr 5;173(2):371-385.e18
pubmed: 29625053
Science. 2012 Dec 14;338(6113):1435-9
pubmed: 23239728
Mol Cell Biol. 2013 Apr;33(7):1317-30
pubmed: 23358416
Nat Rev Cancer. 2021 Aug;21(8):500-509
pubmed: 34230647
Nat Rev Genet. 2016 Feb;17(2):93-108
pubmed: 26781813
Blood. 2002 Jul 1;100(1):246-58
pubmed: 12070034
Nature. 1986 Oct 16-22;323(6089):643-6
pubmed: 2877398
J Pathol. 2011 Jan;223(2):137-46
pubmed: 21125671
Nat Genet. 2004 Aug;36(8):867-71
pubmed: 15235602
Nature. 1992 Sep 24;359(6393):288-94
pubmed: 1406932
Nat Commun. 2022 Jan 12;13(1):281
pubmed: 35022408
Cell. 2017 Sep 21;171(1):103-119.e18
pubmed: 28938112
Haematologica. 2012 Sep;97(9):1405-13
pubmed: 22491738
Blood. 2006 Dec 15;108(13):4198-201
pubmed: 16926283
Nature. 2005 Jul 14;436(7048):221-6
pubmed: 16015321
Cancer Cell. 2008 Dec 9;14(6):447-57
pubmed: 19061836
Bioinformatics. 2019 Jun 1;35(12):2084-2092
pubmed: 30395178
Nat Rev Cancer. 2020 Oct;20(10):573-593
pubmed: 32636489
EMBO J. 1998 Aug 17;17(16):4657-67
pubmed: 9707425
Leukemia. 2018 Jun;32(6):1358-1369
pubmed: 29740158
Nat Immunol. 2017 Apr;18(4):433-441
pubmed: 28250424
Nat Genet. 2014 Apr;46(4):364-70
pubmed: 24584072
Nat Commun. 2017 Feb 09;8:14385
pubmed: 28181482
Nat Genet. 2017 May;49(5):730-741
pubmed: 28319090
Nature. 2017 Dec 7;552(7683):121-125
pubmed: 29143824
Science. 2014 Aug 22;345(6199):943-9
pubmed: 25103404
Nature. 2014 Nov 20;515(7527):355-64
pubmed: 25409824
Science. 2016 Mar 25;351(6280):1454-1458
pubmed: 26940867
Cell. 2019 Feb 7;176(4):897-912.e20
pubmed: 30686579
Blood. 2012 May 10;119(19):4476-9
pubmed: 22438252
Nat Med. 2014 Oct;20(10):1130-7
pubmed: 25194570
Cancer Cell. 2013 Jul 8;24(1):15-29
pubmed: 23845441
Cell. 2011 Jan 21;144(2):296-309
pubmed: 21241896
Lancet Oncol. 2009 Feb;10(2):147-56
pubmed: 19147408
Nat Rev Cancer. 2016 Jul 25;16(8):494-507
pubmed: 27451956
Nat Genet. 2010 May;42(5):454-8
pubmed: 20400965
Nature. 2005 Jul 14;436(7048):272-6
pubmed: 16015333
Nucleic Acids Res. 2017 Nov 16;45(20):12054
pubmed: 29036333
Sci Rep. 2016 May 09;6:25533
pubmed: 27156886
Nucleic Acids Res. 2021 Feb 22;49(3):e15
pubmed: 33275159
Nature. 2009 Apr 9;458(7239):719-24
pubmed: 19360079
Mol Cancer. 2017 Aug 23;16(1):142
pubmed: 28830551
Nature. 2018 Oct;562(7728):526-531
pubmed: 30333627
Cell. 2017 Oct 5;171(2):481-494.e15
pubmed: 28985567
Cancer Discov. 2021 Dec 1;11(12):3158-3177
pubmed: 34282029
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Blood. 2016 May 19;127(20):2391-405
pubmed: 27069254
Genes Dev. 2017 Dec 1;31(23-24):2343-2360
pubmed: 29326336
Sci Rep. 2017 Mar 02;7:43613
pubmed: 28252665
Mol Cell. 2010 May 28;38(4):576-89
pubmed: 20513432
Nat Methods. 2012 Feb 28;9(3):215-6
pubmed: 22373907
Cell. 2017 Feb 9;168(4):629-643
pubmed: 28187285
Immunity. 2018 Feb 20;48(2):227-242.e8
pubmed: 29466755
Science. 1999 Sep 24;285(5436):2122-5
pubmed: 10497129
Science. 2010 Nov 19;330(6007):1104-7
pubmed: 20947725
Immunity. 2011 Aug 26;35(2):299-311
pubmed: 21867929
Nucleic Acids Res. 2017 Jan 4;45(D1):D896-D901
pubmed: 27899670
Cell. 2022 Feb 3;185(3):563-575.e11
pubmed: 35120664
PLoS Genet. 2014 Apr 10;10(4):e1004250
pubmed: 24721906
Blood. 2009 Jul 16;114(3):647-50
pubmed: 19458356
Leuk Lymphoma. 2011 Feb;52(2):290-7
pubmed: 21261500
Blood. 2016 Apr 14;127(15):1863-9
pubmed: 26747249
Front Cell Neurosci. 2017 Mar 29;11:89
pubmed: 28424591
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W187-91
pubmed: 24799436
Nature. 2014 Jul 31;511(7511):616-20
pubmed: 25043025
Mol Ther. 2016 Mar;24(3):592-606
pubmed: 26755332
Nature. 2020 Feb;578(7793):102-111
pubmed: 32025015
Nat Genet. 2019 Dec;51(12):1664-1669
pubmed: 31784727
Nat Med. 2007 Oct;13(10):1203-10
pubmed: 17873882
Leukemia. 2017 Oct;31(10):2057-2064
pubmed: 28260788
Blood Cancer Discov. 2021 Jan;2(1):92-109
pubmed: 33458694
Nature. 2018 Feb 1;554(7690):62-68
pubmed: 29364867
Curr Opin Hematol. 2013 Jul;20(4):369-73
pubmed: 23695450
Bioinformatics. 2015 Nov 1;31(21):3555-7
pubmed: 26139635
Immunity. 2018 Feb 20;48(2):243-257.e10
pubmed: 29466756
Nat Protoc. 2017 Feb;12(2):289-309
pubmed: 28079877
Nucleic Acids Res. 2023 Feb 28;51(4):e21
pubmed: 36617985
Cancer Cell. 2011 Apr 12;19(4):484-97
pubmed: 21481790
Genome Res. 2010 May;20(5):623-35
pubmed: 20308636
Science. 2014 Dec 12;346(6215):1373-7
pubmed: 25394790
Nat Immunol. 2020 Sep;21(9):1010-1021
pubmed: 32661362
Nature. 2012 Jan 11;481(7380):157-63
pubmed: 22237106