The genomic landscape of metastatic clear cell renal cell carcinoma after systemic therapy.
VEGF
cancer
genomics
immunotherapy
kidney
metastasis
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
revised:
03
02
2022
received:
17
06
2021
accepted:
28
02
2022
pubmed:
2
3
2022
medline:
22
6
2022
entrez:
1
3
2022
Statut:
ppublish
Résumé
Primary clear cell renal cell carcinoma (ccRCC) has been previously characterized, but the genomic landscape of metastatic ccRCC is largely unexplored. Here, we performed whole exome sequencing (WES) in 68 samples from 44 patients with ccRCC, including 52 samples from a metastatic site. SETD2, PBRM1, APC and VHL were the most frequently mutated genes in the metastatic ccRCC cohort. RBM10 and FBXW7 were also among the 10 most frequently mutated genes in metastatic tissues. Recurrent somatic copy number variations (CNV) were observed at the previously identified regions 3p25, 9p21 and 14q25, but also at 6p21 (CDKN1A) and 13q14 (RB1). No statistically significant differences were found between samples from therapy-naïve and pretreated patients. Clonal evolution analyses with multiple samples from 13 patients suggested that early appearance of CNVs at 3p25, 9p21 and 14q25 may be associated with rapid clinical progression. Overall, the genomic landscapes of primary and metastatic ccRCC seem to share frequent CNVs at 3p25, 9p21 and 14q25. Future work will clarify the implication of RBM10 and FBXW7 mutations and 6p21 and 13q14 CNVs in metastatic ccRCC.
Identifiants
pubmed: 35231161
doi: 10.1002/1878-0261.13204
pmc: PMC9208073
doi:
Substances chimiques
F-Box-WD Repeat-Containing Protein 7
0
Nuclear Proteins
0
RBM10 protein, human
0
RNA-Binding Proteins
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
2384-2395Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK113088
Pays : United States
Informations de copyright
© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
Références
PLoS One. 2012;7(7):e40332
pubmed: 22808135
Br J Cancer. 2018 May;118(9):1238-1242
pubmed: 29674707
J Clin Oncol. 2012 Sep 1;30(25):3077-83
pubmed: 22826274
N Engl J Med. 2012 Mar 8;366(10):883-892
pubmed: 22397650
Drug Resist Updat. 2014 Oct-Dec;17(4-6):77-88
pubmed: 25457974
Front Oncol. 2021 Jul 21;11:677826
pubmed: 34367963
Nature. 2013 Jul 4;499(7456):43-9
pubmed: 23792563
JAMA Oncol. 2015 Jul;1(4):466-74
pubmed: 26181256
Mol Cancer. 2018 Aug 7;17(1):115
pubmed: 30086763
Lancet Oncol. 2013 Feb;14(2):141-8
pubmed: 23312463
Cancer Res. 2009 Jun 1;69(11):4674-81
pubmed: 19470766
Nat Genet. 2012 Jun 10;44(7):751-9
pubmed: 22683710
Nat Genet. 2014 Mar;46(3):225-233
pubmed: 24487277
Cancer Cell. 2021 Nov 8;39(11):1497-1518.e11
pubmed: 34715028
Nature. 2013 Jul 11;499(7457):214-218
pubmed: 23770567
Mol Cell. 2020 Oct 15;80(2):183-192
pubmed: 32946743
Oncogenesis. 2012 Jun 25;1:e14
pubmed: 23552698
J Natl Compr Canc Netw. 2016 Jul;14(7):820-4
pubmed: 27407122
Eur Urol. 2017 Mar;71(3):405-414
pubmed: 27751729
Bioinformatics. 2010 Mar 1;26(5):589-95
pubmed: 20080505
Cancer Discov. 2020 Sep;10(9):1296-1311
pubmed: 32371478
Am J Surg Pathol. 2020 Jul;44(7):e47-e65
pubmed: 32251007
Clin Cancer Res. 2018 Sep 1;24(17):4137-4144
pubmed: 29760223
Nat Rev Clin Oncol. 2021 Apr;18(4):199-214
pubmed: 33437048
Lancet Oncol. 2018 Dec;19(12):1688-1698
pubmed: 30416077
Cell. 2018 Apr 19;173(3):595-610.e11
pubmed: 29656894
Ann Oncol. 2010 Aug;21(8):1599-1606
pubmed: 20089566
Genome Biol. 2014 Aug 26;15(8):439
pubmed: 25160065
NPJ Genom Med. 2016;1:
pubmed: 28781886
Nat Genet. 2013 Aug;45(8):860-7
pubmed: 23797736
Bioinformatics. 2011 Nov 1;27(21):2987-93
pubmed: 21903627
Cancer Cell. 2021 May 10;39(5):649-661.e5
pubmed: 33711272
Cell. 2018 Apr 19;173(3):581-594.e12
pubmed: 29656895
Nat Med. 2020 Jun;26(6):909-918
pubmed: 32472114
Nat Med. 2013 Jan;19(1):50-6
pubmed: 23223005
JCO Precis Oncol. 2017;2017:
pubmed: 29333526
Eur Urol Focus. 2018 Dec;4(6):986-994
pubmed: 29066084
Nat Commun. 2014 Oct 29;5:5135
pubmed: 25351205