Multi-omics comparison of malignant and normal uveal melanocytes reveals molecular features of uveal melanoma.
BAP1
CP: Cancer
PRAME
genome instability
multi-omics
uveal melanoma
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
26 09 2023
26 09 2023
Historique:
received:
12
01
2023
revised:
10
07
2023
accepted:
30
08
2023
medline:
26
10
2023
pubmed:
14
9
2023
entrez:
14
9
2023
Statut:
ppublish
Résumé
Uveal melanoma (UM) is a rare cancer resulting from the transformation of melanocytes in the uveal tract. Integrative analysis has identified four molecular and clinical subsets of UM. To improve our molecular understanding of UM, we performed extensive multi-omics characterization comparing two aggressive UM patient-derived xenograft models with normal choroidal melanocytes, including DNA optical mapping, specific histone modifications, and DNA topology analysis using Hi-C. Our gene expression and cytogenetic analyses suggest that genomic instability is a hallmark of UM. We also identified a recurrent deletion in the BAP1 promoter resulting in loss of expression and associated with high risk of metastases in UM patients. Hi-C revealed chromatin topology changes associated with the upregulation of PRAME, an independent prognostic biomarker in UM, and a potential therapeutic target. Our findings illustrate how multi-omics approaches can improve our understanding of tumorigenesis and reveal two distinct mechanisms of gene expression dysregulation in UM.
Identifiants
pubmed: 37708024
pii: S2211-1247(23)01144-0
doi: 10.1016/j.celrep.2023.113132
pmc: PMC10598242
mid: NIHMS1933915
pii:
doi:
Substances chimiques
DNA
9007-49-2
PRAME protein, human
0
Antigens, Neoplasm
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
113132Subventions
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG003143
Pays : United States
Organisme : NHGRI NIH HHS
ID : R13 HG003431
Pays : United States
Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests P.d.l.G. is a co-founder of Genosplice technology. A.J. and R.G. are employees of Genosplice technology. R.M. is the founder of Cell Environment.
Références
Clin Cancer Res. 2016 Mar 1;22(5):1234-42
pubmed: 26933176
Clin Cancer Res. 2019 Sep 15;25(18):5513-5524
pubmed: 31227496
Nucleic Acids Res. 2022 Jan 7;50(D1):D687-D692
pubmed: 34788843
Cancer Cell. 2017 May 8;31(5):685-696.e6
pubmed: 28486107
Invest Ophthalmol Vis Sci. 2012 May 14;53(6):2668-74
pubmed: 22427574
Nature. 2009 Jan 29;457(7229):599-602
pubmed: 19078957
Br J Ophthalmol. 2014 Jun;98(6):769-74
pubmed: 24169649
FASEB J. 2019 Sep;33(9):10490-10504
pubmed: 31311326
Am J Hum Genet. 2016 Nov 3;99(5):1190-1198
pubmed: 27745836
Methods Mol Biol. 2012;859:29-51
pubmed: 22367864
Ophthalmology. 2016 May;123(5):1118-28
pubmed: 26923342
Trans Am Ophthalmol Soc. 2016 Aug;114:T5
pubmed: 28018010
Mol Oncol. 2013 Jun;7(3):625-36
pubmed: 23478236
BMC Genomics. 2019 Apr 18;19(Suppl 9):985
pubmed: 30999860
Mol Cell. 2021 Aug 5;81(15):3082-3095.e6
pubmed: 34197738
Science. 2009 Oct 9;326(5950):289-93
pubmed: 19815776
Cell. 2017 Oct 5;171(2):305-320.e24
pubmed: 28985562
Nat Genet. 2018 Oct;50(10):1388-1398
pubmed: 30202056
Nat Commun. 2016 Feb 04;7:10615
pubmed: 26842708
N Engl J Med. 2010 Dec 2;363(23):2191-9
pubmed: 21083380
Nat Biotechnol. 2012 Aug;30(8):771-6
pubmed: 22797562
Cell. 2014 Dec 18;159(7):1665-80
pubmed: 25497547
Lab Invest. 2013 May;93(5):611-21
pubmed: 23459372
Cancer Cell. 2017 Aug 14;32(2):204-220.e15
pubmed: 28810145
Cell Rep. 2016 May 31;15(9):2038-49
pubmed: 27210764
Eur J Hum Genet. 2012 Nov;20(11):1141-7
pubmed: 22549408
Oncotarget. 2016 Jan 26;7(4):4624-31
pubmed: 26683228
Elife. 2013 Dec 31;2:e01749
pubmed: 24381249
Nucleic Acids Res. 2018 Jan 4;46(D1):D794-D801
pubmed: 29126249
Nat Genet. 2013 Feb;45(2):133-5
pubmed: 23313955
Quant Biol. 2019 Dec 31;7(4):327-334
pubmed: 34084562
Mol Oncol. 2014 Dec;8(8):1508-20
pubmed: 24994677
Nature. 1983 Jan 6;301(5895):89-92
pubmed: 6185846
Cancers (Basel). 2018 May 30;10(6):
pubmed: 29848986
Nature. 2012 Sep 6;489(7414):57-74
pubmed: 22955616
Nature. 2012 Apr 11;485(7398):381-5
pubmed: 22495304
Oncotarget. 2016 Sep 13;7(37):59209-59219
pubmed: 27486988
Oncogenesis. 2020 Mar 2;9(3):29
pubmed: 32123162
BMC Bioinformatics. 2018 Sep 6;19(1):313
pubmed: 30189838
Genes Chromosomes Cancer. 2007 Sep;46(9):796-804
pubmed: 17534929
Pigment Cell Melanoma Res. 2012 Mar;25(2):182-7
pubmed: 22236444
Methods Mol Biol. 2018;1767:311-349
pubmed: 29524144
Nature. 2015 Jul 9;523(7559):240-4
pubmed: 26030525
Cell Rep. 2018 Feb 27;22(9):2455-2468
pubmed: 29490280
Mutat Res. 2014 Dec;770:45-53
pubmed: 25771869
Genome Med. 2018 Mar 28;10(1):25
pubmed: 29592813
Genes (Basel). 2020 Apr 27;11(5):
pubmed: 32349350
Methods Mol Biol. 2018;1833:193-203
pubmed: 30039375
J Mol Biol. 2007 Sep 14;372(2):298-316
pubmed: 17663992
Clin Ophthalmol. 2017 Jan 31;11:279-289
pubmed: 28203054
Science. 2010 Dec 3;330(6009):1410-3
pubmed: 21051595
Genome Biol. 2015 Dec 01;16:259
pubmed: 26619908
Pigment Cell Melanoma Res. 2017 May;30(3):317-327
pubmed: 28140525
Nat Genet. 2016 Jun;48(6):675-80
pubmed: 27089179
Biomark Res. 2020 Dec 9;8(1):71
pubmed: 33298164
Nucleic Acids Res. 1983 Oct 11;11(19):6883-94
pubmed: 6314264
Bioinformatics. 2019 Jun 1;35(11):1978-1980
pubmed: 30376034
Clin Cancer Res. 2010 Apr 15;16(8):2352-62
pubmed: 20371695
Nat Commun. 2021 May 10;12(1):2439
pubmed: 33972523
Cell Res. 2008 Nov;18(11):1128-40
pubmed: 18957938
Nat Genet. 2013 Aug;45(8):933-6
pubmed: 23793026
Oncogene. 2021 Jan;40(4):806-820
pubmed: 33262460