Mesenchymal tumor organoid models recapitulate rhabdomyosarcoma subtypes.
CRISPR/Cas9
drug screening
mesenchymal
rhabdomyosarcoma
tumoroid
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
10 10 2022
10 10 2022
Historique:
revised:
11
07
2022
received:
11
03
2022
accepted:
12
07
2022
pubmed:
3
8
2022
medline:
12
10
2022
entrez:
2
8
2022
Statut:
ppublish
Résumé
Rhabdomyosarcomas (RMS) are mesenchyme-derived tumors and the most common childhood soft tissue sarcomas. Treatment is intense, with a nevertheless poor prognosis for high-risk patients. Discovery of new therapies would benefit from additional preclinical models. Here, we describe the generation of a collection of 19 pediatric RMS tumor organoid (tumoroid) models (success rate of 41%) comprising all major subtypes. For aggressive tumors, tumoroid models can often be established within 4-8 weeks, indicating the feasibility of personalized drug screening. Molecular, genetic, and histological characterization show that the models closely resemble the original tumors, with genetic stability over extended culture periods of up to 6 months. Importantly, drug screening reflects established sensitivities and the models can be modified by CRISPR/Cas9 with TP53 knockout in an embryonal RMS model resulting in replicative stress drug sensitivity. Tumors of mesenchymal origin can therefore be used to generate organoid models, relevant for a variety of preclinical and clinical research questions.
Identifiants
pubmed: 35916583
doi: 10.15252/emmm.202216001
pmc: PMC9549731
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e16001Informations de copyright
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.
Références
Surgery. 1962 Oct;52:572-84
pubmed: 14484432
Arch Med Res. 2014 Feb;45(2):143-51
pubmed: 24486246
Lancet Oncol. 2019 Nov;20(11):1566-1575
pubmed: 31562043
Science. 2012 Aug 17;337(6096):816-21
pubmed: 22745249
Nat Rev Dis Primers. 2019 Jan 7;5(1):1
pubmed: 30617281
Clin Sarcoma Res. 2012 Oct 04;2(1):14
pubmed: 23036164
Eur J Cancer. 2008 Apr;44(6):876-84
pubmed: 18342500
Nat Med. 2010 Feb;16(2):171-3
pubmed: 20134473
Genome Biol. 2019 Oct 21;20(1):213
pubmed: 31639029
Nucleic Acids Res. 2014 Dec 16;42(22):e168
pubmed: 25300484
Nat Protoc. 2018 Feb;13(2):235-247
pubmed: 29300390
Front Oncol. 2013 Jul 17;3:183
pubmed: 23882450
Sci Transl Med. 2018 Jul 4;10(448):
pubmed: 29973406
Nat Rev Cancer. 2015 Jul;15(7):426-39
pubmed: 26105539
Stem Cell Investig. 2014 Oct 27;1:18
pubmed: 27358864
Nature. 2009 May 14;459(7244):262-5
pubmed: 19329995
J Exp Clin Cancer Res. 2016 Dec 5;35(1):189
pubmed: 27919280
Nat Commun. 2020 Mar 11;11(1):1310
pubmed: 32161258
Clin Cancer Res. 2011 Dec 1;17(23):7324-36
pubmed: 21948088
Neuro Oncol. 2022 Apr 1;24(4):612-623
pubmed: 34850183
J Clin Med. 2021 Apr 08;10(8):
pubmed: 33918045
Sci Rep. 2021 Aug 17;11(1):16668
pubmed: 34404908
J Clin Oncol. 2021 Sep 20;39(27):2979-2990
pubmed: 34343032
J Clin Oncol. 2021 Sep 10;39(26):2859-2871
pubmed: 34166060
Cell Rep. 2020 May 5;31(5):107588
pubmed: 32375033
BMC Cancer. 2019 Oct 21;19(1):970
pubmed: 31638925
Gastroenterology. 2011 Nov;141(5):1762-72
pubmed: 21889923
Cell. 2016 Jun 16;165(7):1586-1597
pubmed: 27315476
Nat Commun. 2019 Jul 5;10(1):2969
pubmed: 31278357
Pediatrics. 2008 Jun;121(6):e1470-7
pubmed: 18519450
Cell Death Dis. 2019 Feb 27;10(3):201
pubmed: 30814510
JCO Precis Oncol. 2021 Oct 27;5:
pubmed: 34738048
Neuro Oncol. 2021 Nov 2;23(11):1936-1948
pubmed: 34214169
Nat Med. 2015 Nov;21(11):1318-25
pubmed: 26479923
Cell. 2019 Jun 13;177(7):1903-1914.e14
pubmed: 31031007
J Clin Oncol. 1999 Nov;17(11):3487-93
pubmed: 10550146
Cell. 2021 Jun 24;184(13):3573-3587.e29
pubmed: 34062119
Am J Pathol. 2000 Feb;156(2):399-408
pubmed: 10666368
Cell. 2020 Jan 9;180(1):188-204.e22
pubmed: 31883794
Cancer Cell. 2018 Jan 8;33(1):108-124.e5
pubmed: 29316425
Am J Surg Pathol. 2019 Jun;43(6):747-754
pubmed: 30829729
Nat Commun. 2021 Mar 3;12(1):1407
pubmed: 33658498
Cancer Res. 1996 Jul 15;56(14):3220-4
pubmed: 8764111
Mod Pathol. 2007 Apr;20(4):482-96
pubmed: 17334349
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Bioinformatics. 2014 Jul 15;30(14):2076-8
pubmed: 24681907
Nature. 2017 Sep 7;549(7670):96-100
pubmed: 28854174
Nature. 1991 Jul 25;352(6333):345-7
pubmed: 1852210
Cell. 2015 May 7;161(4):933-45
pubmed: 25957691
Cancer. 2019 Aug 1;125(15):2602-2609
pubmed: 31067356
Nat Rev Drug Discov. 2015 Jun;14(6):405-23
pubmed: 25953507
Lancet Oncol. 2018 Feb;19(2):207-215
pubmed: 29361470
Br J Cancer. 2019 Feb;120(4):435-443
pubmed: 30745580
Nature. 2020 Feb;578(7793):94-101
pubmed: 32025018
Cancer Res. 2004 Aug 15;64(16):5539-45
pubmed: 15313887
Cell. 2019 Mar 7;176(6):1282-1294.e20
pubmed: 30849372
Nat Commun. 2020 Sep 15;11(1):4629
pubmed: 32934208
J Surg Res. 2011 Oct;170(2):e243-51
pubmed: 21529833
J Clin Invest. 2012 Apr;122(4):1541-52
pubmed: 22446188
EMBO Mol Med. 2022 Oct 10;14(10):e16001
pubmed: 35916583
Nucleic Acids Res. 2019 May 7;47(8):e47
pubmed: 30783653
Arch Pathol Lab Med. 2015 Oct;139(10):1281-7
pubmed: 25989287
Bioinformatics. 2011 Aug 1;27(15):2156-8
pubmed: 21653522
Nat Protoc. 2021 Apr;16(4):1936-1965
pubmed: 33692550
Nature. 2015 May 7;521(7550):43-7
pubmed: 25924068
Cancer Discov. 2014 Feb;4(2):216-31
pubmed: 24436047
Nat Rev Mol Cell Biol. 2020 Oct;21(10):571-584
pubmed: 32636524
Life Sci Alliance. 2020 Dec 23;4(2):
pubmed: 33361335
Clin Cancer Res. 2020 Mar 1;26(5):1135-1140
pubmed: 31699828
Cell. 2019 May 2;177(4):821-836.e16
pubmed: 30982602
Genome Med. 2018 Apr 25;10(1):33
pubmed: 29695279
BMC Genomics. 2022 Feb 15;23(1):134
pubmed: 35168570
PLoS One. 2015 Dec 30;10(12):e0146021
pubmed: 26717316
Trends Immunol. 2020 Aug;41(8):652-664
pubmed: 32654925
Cell Syst. 2016 Oct 26;3(4):385-394.e3
pubmed: 27693023
Eur J Cancer. 2021 Jul;151:84-93
pubmed: 33971448
Am J Surg Pathol. 2008 Oct;32(10):1513-22
pubmed: 18708938
EMBO Mol Med. 2017 Feb;9(2):137-153
pubmed: 28028012
J Biol Chem. 1998 Mar 6;273(10):5858-68
pubmed: 9488723
EMBO J. 2019 Aug 1;38(15):e101654
pubmed: 31282586
Cancers (Basel). 2020 Sep 18;12(9):
pubmed: 32962010
Gigascience. 2018 Jun 1;7(6):
pubmed: 29846586
Nature. 2012 Jan 18;481(7381):306-13
pubmed: 22258609
Am J Clin Pathol. 1958 Apr;29(4):356-66
pubmed: 13533329