Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 02 2023
28 02 2023
Historique:
received:
05
05
2022
accepted:
16
02
2023
entrez:
28
2
2023
pubmed:
1
3
2023
medline:
3
3
2023
Statut:
epublish
Résumé
The mechanisms triggering metastasis in pheochromocytoma/paraganglioma are unknown, hindering therapeutic options for patients with metastatic tumors (mPPGL). Herein we show by genomic profiling of a large cohort of mPPGLs that high mutational load, microsatellite instability and somatic copy-number alteration burden are associated with ATRX/TERT alterations and are suitable prognostic markers. Transcriptomic analysis defines the signaling networks involved in the acquisition of metastatic competence and establishes a gene signature related to mPPGLs, highlighting CDK1 as an additional mPPGL marker. Immunogenomics accompanied by immunohistochemistry identifies a heterogeneous ecosystem at the tumor microenvironment level, linked to the genomic subtype and tumor behavior. Specifically, we define a general immunosuppressive microenvironment in mPPGLs, the exception being PD-L1 expressing MAML3-related tumors. Our study reveals canonical markers for risk of metastasis, and suggests the usefulness of including immune parameters in clinical management for PPGL prognostication and identification of patients who might benefit from immunotherapy.
Identifiants
pubmed: 36854674
doi: 10.1038/s41467-023-36769-6
pii: 10.1038/s41467-023-36769-6
pmc: PMC9975198
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1122Informations de copyright
© 2023. The Author(s).
Références
Nat Commun. 2015 Jan 27;6:6044
pubmed: 25625332
Ann Oncol. 2018 Jan 1;29(1):84-91
pubmed: 29228097
Nat Biotechnol. 2019 Jul;37(7):773-782
pubmed: 31061481
Br J Cancer. 2019 Jan;120(1):45-53
pubmed: 30413828
J Neuroimmune Pharmacol. 2013 Mar;8(1):7-14
pubmed: 22886869
Nature. 2013 Jul 11;499(7457):214-218
pubmed: 23770567
Cancers (Basel). 2019 May 16;11(5):
pubmed: 31100940
Bioinformatics. 2012 Mar 15;28(6):882-3
pubmed: 22257669
Nucleic Acids Res. 2016 Sep 19;44(16):e131
pubmed: 27270079
Endocr Relat Cancer. 2020 Aug;27(8):T41-T52
pubmed: 32069214
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Oncotarget. 2017 Jan 31;8(5):7452-7463
pubmed: 27980218
Cancers (Basel). 2020 Aug 16;12(8):
pubmed: 32824391
Biostatistics. 2007 Jan;8(1):118-27
pubmed: 16632515
Cancer Cell. 2021 Jun 14;39(6):845-865.e7
pubmed: 34019806
Endocr Pathol. 2019 Jun;30(2):90-95
pubmed: 31001800
Genome Biol. 2011;12(4):R41
pubmed: 21527027
Nat Med. 2019 May;25(5):767-775
pubmed: 31011208
Int J Mol Sci. 2019 Oct 07;20(19):
pubmed: 31591367
Int J Mol Sci. 2018 Oct 04;19(10):
pubmed: 30287763
Nat Commun. 2022 Oct 21;13(1):6262
pubmed: 36271074
Nat Biotechnol. 2013 Mar;31(3):213-9
pubmed: 23396013
Biochim Biophys Acta. 2014 Apr;1845(2):182-201
pubmed: 24440852
Endocr Relat Cancer. 2014 May 06;21(3):427-34
pubmed: 24803525
Science. 2017 Sep 29;357(6358):1416-1420
pubmed: 28818973
J Exp Med. 2020 Nov 2;217(11):
pubmed: 32860047
Genome Biol. 2016 Jun 06;17(1):122
pubmed: 27268795
Nat Rev Cancer. 2018 Jan;18(1):51-63
pubmed: 29192214
Nat Rev Drug Discov. 2018 Dec;17(12):887-904
pubmed: 30361552
Genome Biol. 2014;15(12):550
pubmed: 25516281
JCO Precis Oncol. 2017;2017:
pubmed: 29850653
Oncoimmunology. 2013 Aug 1;2(8):e25419
pubmed: 24167765
Mol Cell Biol. 2001 Jul;21(13):4246-55
pubmed: 11390653
Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):1999-2004
pubmed: 23345422
Hum Genet. 2016 Mar;135(3):359-62
pubmed: 26742503
Int J Cancer. 2016 May 1;138(9):2201-11
pubmed: 26650627
Nat Biotechnol. 2015 Nov;33(11):1152-8
pubmed: 26372948
F1000Res. 2020 Aug 24;9:1028
pubmed: 33214875
Endocr Relat Cancer. 2013 Jun 24;20(4):477-93
pubmed: 23660872
Cell Metab. 2016 Nov 8;24(5):657-671
pubmed: 27641098
Nat Rev Clin Oncol. 2017 Dec;14(12):717-734
pubmed: 28741618
Endocr Pathol. 2022 Mar;33(1):90-114
pubmed: 35285002
Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20467-72
pubmed: 23169665
Br J Haematol. 2001 Aug;114(2):307-12
pubmed: 11529848
Nature. 2014 Nov 27;515(7528):568-71
pubmed: 25428505
Nucleic Acids Res. 2013 Jan;41(Database issue):D377-86
pubmed: 23193289
Sci Rep. 2017 Dec 4;7(1):16878
pubmed: 29203879
Clin Cancer Res. 2019 May 15;25(10):3074-3083
pubmed: 30635339
Science. 2016 Apr 8;352(6282):227-31
pubmed: 26966191
Nat Genet. 2018 Sep;50(9):1262-1270
pubmed: 30104763
Nat Med. 2018 May;24(5):541-550
pubmed: 29686425
Endocr Relat Cancer. 2019 Jan 1;26(1):165-180
pubmed: 30345732
Cancer Cell. 2017 Feb 13;31(2):159-161
pubmed: 28196587
Cancers (Basel). 2019 May 11;11(5):
pubmed: 31083581
Endocr Relat Cancer. 2010 Jun 03;17(3):561-79
pubmed: 20410162
Nat Rev Cancer. 2017 Jan 27;17(2):93-115
pubmed: 28127048
Nat Rev Clin Oncol. 2022 Jan;19(1):37-50
pubmed: 34580473
Cancer Immunol Res. 2020 Mar;8(3):409-420
pubmed: 31907209
Oncotarget. 2015 Oct 20;6(32):32955-65
pubmed: 26460615
Ann Endocrinol (Paris). 2019 Jun;80(3):159-162
pubmed: 31053249
Immunity. 2018 Apr 17;48(4):812-830.e14
pubmed: 29628290
Hum Mol Genet. 2011 Oct 15;20(20):3974-85
pubmed: 21784903
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Int J Cancer. 2007 Sep 15;121(6):1386-9
pubmed: 17520677
Nat Genet. 2017 Mar;49(3):349-357
pubmed: 28135248
Nucleic Acids Res. 2019 Jan 8;47(D1):D607-D613
pubmed: 30476243
Endocr Relat Cancer. 2014 May 06;21(3):405-14
pubmed: 24521857
Endocr Pathol. 2012 Mar;23(1):34-42
pubmed: 22183643
Front Endocrinol (Lausanne). 2020 Nov 10;11:587779
pubmed: 33244312
Cancer Cell. 2017 Feb 13;31(2):181-193
pubmed: 28162975
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Nat Rev Cancer. 2012 Mar 15;12(4):298-306
pubmed: 22419253
Cancers (Basel). 2021 Sep 23;13(19):
pubmed: 34638246
Nat Rev Cancer. 2014 Dec;14(12):786-800
pubmed: 25568919
Nat Rev Immunol. 2020 Nov;20(11):651-668
pubmed: 32433532
BMC Bioinformatics. 2013 Jan 16;14:7
pubmed: 23323831
Nat Biotechnol. 2011 Jan;29(1):24-6
pubmed: 21221095
Endocr Rev. 2017 Dec 1;38(6):489-515
pubmed: 28938417
Lancet Oncol. 2013 May;14(6):534-42
pubmed: 23598174
Nat Rev Immunol. 2006 Apr;6(4):295-307
pubmed: 16557261
Nat Rev Cancer. 2013 May;13(5):357-65
pubmed: 23612461
Endocr Relat Cancer. 2016 Apr;23(4):281-93
pubmed: 26911374
Genome Biol. 2013 Apr 25;14(4):R36
pubmed: 23618408
Ann Oncol. 2020 Nov;31(11):1476-1490
pubmed: 32861807
Elife. 2018 Sep 04;7:
pubmed: 30178746
Cell Metab. 2019 Jul 2;30(1):36-50
pubmed: 31269428
Nat Rev Cancer. 2020 Nov;20(11):662-680
pubmed: 32753728
Nat Commun. 2015 Jan 21;6:6140
pubmed: 25608029
Cell Rep. 2013 Jul 11;4(1):87-98
pubmed: 23831031
Nat Commun. 2017 Jun 06;8:15180
pubmed: 28585546
J Med Genet. 2019 Aug;56(8):513-520
pubmed: 30877234
Nat Commun. 2013;4:2612
pubmed: 24113773
J Clin Endocrinol Metab. 2019 Jun 1;104(6):2367-2374
pubmed: 30715419
J Pathol. 2023 Jan;259(1):103-114
pubmed: 36314599
Endocr Rev. 2022 Mar 9;43(2):199-239
pubmed: 34147030
Theranostics. 2019 Jul 9;9(17):4946-4958
pubmed: 31410193
Clin Cancer Res. 2019 Jan 15;25(2):760-770
pubmed: 30301828
Bioinformatics. 2005 Aug 15;21(16):3439-40
pubmed: 16082012
Nature. 2007 Aug 16;448(7155):811-5
pubmed: 17700700
Endocr Relat Cancer. 2014 Aug;21(4):653-61
pubmed: 24951106
J Clin Invest. 2019 Jul 22;129(8):3435-3447
pubmed: 31329159