CRISPR-mediated modeling and functional validation of candidate tumor suppressor genes in small cell lung cancer.
Animals
Apoptosis
/ genetics
CRISPR-Cas Systems
/ genetics
Cell Line
Cell Proliferation
/ genetics
Disease Models, Animal
Disease Progression
Feasibility Studies
Gene Editing
/ methods
Gene Expression Regulation, Neoplastic
Genes, Tumor Suppressor
Humans
Loss of Function Mutation
Lung
/ pathology
Lung Neoplasms
/ genetics
Mice
Mice, Transgenic
Neoplasm Staging
Retinoblastoma-Like Protein p107
/ genetics
Retinoblastoma-Like Protein p130
/ genetics
Small Cell Lung Carcinoma
/ genetics
Tumor Burden
/ genetics
Tumor Suppressor Protein p53
/ genetics
CRISPR
GEMM
p107
small cell lung cancer
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
07 01 2020
07 01 2020
Historique:
pubmed:
25
12
2019
medline:
6
5
2020
entrez:
25
12
2019
Statut:
ppublish
Résumé
Small cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer that remains among the most lethal of solid tumor malignancies. Recent genomic sequencing studies have identified many recurrently mutated genes in human SCLC tumors. However, the functional roles of most of these genes remain to be validated. Here, we have adapted the CRISPR-Cas9 system to a well-established murine model of SCLC to rapidly model loss-of-function mutations in candidate genes identified from SCLC sequencing studies. We show that loss of the gene
Identifiants
pubmed: 31871154
pii: 1821893117
doi: 10.1073/pnas.1821893117
pmc: PMC6955235
doi:
Substances chimiques
Rbl1 protein, mouse
0
Rbl2 protein, mouse
0
Retinoblastoma-Like Protein p107
0
Retinoblastoma-Like Protein p130
0
Trp53 protein, mouse
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
513-521Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM007753
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014051
Pays : United States
Informations de copyright
Copyright © 2020 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
Competing interest statement: T.J. is a member of the Board of Directors of Amgen and Thermo Fisher Scientific. He is also a co-founder of Dragonfly Therapeutics and T2 Biosystems. T.J. serves on the Scientific Advisory Board of Dragonfly Therapeutics, SQZ Biotech, and Skyhawk Therapeutics. None of these affiliations represent a conflict of interest with respect to the design or execution of this study or interpretation of data presented in this paper. Dr. Jacks’s laboratory currently also receives funding from the Johnson & Johnson Lung Cancer Initiative and Calico, but this funding did not support the research described in this paper.
Références
Nature. 2014 Oct 16;514(7522):380-4
pubmed: 25119044
Nat Protoc. 2009;4(7):1064-72
pubmed: 19561589
Cell. 2013 Jul 18;154(2):442-51
pubmed: 23849981
Nat Rev Cancer. 2015 Jul;15(7):387-95
pubmed: 26040603
Nat Commun. 2017 Jul 10;8:15999
pubmed: 28691711
Genes Dev. 2015 Sep 1;29(17):1850-62
pubmed: 26341558
Genes Dev. 2015 Jul 15;29(14):1576-85
pubmed: 26178787
Nature. 2014 Dec 18;516(7531):428-31
pubmed: 25337879
Cancer Res. 2010 May 15;70(10):3877-83
pubmed: 20406986
Nature. 2013 Jul 11;499(7457):214-218
pubmed: 23770567
Cancer Discov. 2018 Nov;8(11):1422-1437
pubmed: 30181244
Cell. 2016 Jul 14;166(2):328-342
pubmed: 27374332
Nat Methods. 2013 Oct;10(10):973-6
pubmed: 23892895
Mol Cancer Res. 2014 May;12(5):654-9
pubmed: 24482365
Nat Med. 2017 Nov;23(11):1362-1368
pubmed: 28967920
Nat Biotechnol. 2017 Jun;35(6):569-576
pubmed: 28459449
Nat Methods. 2015 Apr;12(4):326-8
pubmed: 25730490
Science. 2016 Jul 29;353(6298):aaf7907
pubmed: 27229144
Genome Biol. 2009;10(3):R25
pubmed: 19261174
Mol Cell. 2014 May 22;54(4):698-710
pubmed: 24837679
BMC Bioinformatics. 2010 Feb 18;11:94
pubmed: 20167110
Nature. 2015 Jan 29;517(7536):583-8
pubmed: 25494202
Cancer Cell. 2017 Feb 13;31(2):270-285
pubmed: 28089889
Cancer Res. 2009 Nov 15;69(22):8733-41
pubmed: 19887614
Nat Genet. 2012 Oct;44(10):1111-6
pubmed: 22941189
Cell Rep. 2016 Jul 19;16(3):631-43
pubmed: 27373156
Nature. 2011 May 5;473(7345):101-4
pubmed: 21471965
Nat Biotechnol. 2016 Feb;34(2):184-191
pubmed: 26780180
Nat Methods. 2017 Feb;14(2):195-200
pubmed: 27918539
Science. 2010 Sep 10;329(5997):1355-8
pubmed: 20829488
Nature. 2017 Jan 5;541(7635):107-111
pubmed: 27869821
Science. 2013 Mar 29;339(6127):1546-58
pubmed: 23539594
Oncotarget. 2016 Sep 6;7(36):57514-57524
pubmed: 27613844
Nat Biotechnol. 2015 Nov;33(11):1159-61
pubmed: 26436575
Cell Growth Differ. 1998 Aug;9(8):585-93
pubmed: 9716176
Cancer. 2015 Mar 1;121(5):664-72
pubmed: 25336398
Sci Rep. 2017 Dec 4;7(1):16878
pubmed: 29203879
Eur Respir J. 2010 Jan;35(1):202-15
pubmed: 20044461
Neural Netw. 2000 May-Jun;13(4-5):411-30
pubmed: 10946390
Immunity. 2018 Oct 16;49(4):764-779.e9
pubmed: 30332632
Cancer Discov. 2016 Feb;6(2):188-201
pubmed: 26586766
Nat Genet. 2012 Oct;44(10):1104-10
pubmed: 22941188
Cell Rep. 2014 Nov 20;9(4):1235-45
pubmed: 25456126
BMC Bioinformatics. 2011 Aug 04;12:323
pubmed: 21816040
Mol Cell Biol. 1996 Dec;16(12):6965-76
pubmed: 8943352
Gene Ther. 2000 Jun;7(12):1034-8
pubmed: 10871752
Cancer Cell. 2003 Sep;4(3):181-9
pubmed: 14522252
Cell. 2014 Oct 23;159(3):635-46
pubmed: 25307933
Annu Rev Immunol. 2015;33:715-45
pubmed: 25861980
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Semin Oncol. 2001 Apr;28(2 Suppl 4):3-13
pubmed: 11479891
J Clin Oncol. 2006 Oct 1;24(28):4539-44
pubmed: 17008692
Nature. 2017 May 18;545(7654):360-364
pubmed: 28489825
Front Immunol. 2016 Jun 22;7:244
pubmed: 27446075
Cancer Discov. 2017 Oct;7(10):1184-1199
pubmed: 28790031
Nat Methods. 2014 Aug;11(8):783-784
pubmed: 25075903
Drugs. 2012 Mar 5;72(4):471-90
pubmed: 22356287
Nature. 2015 Aug 6;524(7563):47-53
pubmed: 26168399
Genes Dev. 2011 Jul 15;25(14):1470-5
pubmed: 21764851
Cell. 2014 Oct 9;159(2):440-55
pubmed: 25263330
Sci Rep. 2016 Feb 18;6:16836
pubmed: 26887506
Cell Metab. 2016 Aug 9;24(2):324-31
pubmed: 27476975
Nature. 2014 Dec 18;516(7531):423-7
pubmed: 25337876
Mol Cancer Res. 2018 May;16(5):825-832
pubmed: 29523765
Science. 2013 Feb 15;339(6121):823-6
pubmed: 23287722
EMBO Mol Med. 2014 Feb;6(2):212-25
pubmed: 24401838
Nat Biotechnol. 2015 Apr;33(4):390-394
pubmed: 25690852
Nat Med. 2017 Mar;23(3):291-300
pubmed: 28191885
Front Immunol. 2016 Oct 03;7:407
pubmed: 27752258
Science. 2013 Feb 15;339(6121):819-23
pubmed: 23287718
Cell. 2017 Dec 14;171(7):1495-1507.e15
pubmed: 29224783
Cell Div. 2010 Apr 02;5:9
pubmed: 20359370
Elife. 2013 Jan 29;2:e00471
pubmed: 23386978
Cell. 2014 Mar 13;156(6):1298-1311
pubmed: 24630729