Transcriptomes of Prostate Cancer with TMPRSS2:ERG and Other ETS Fusions.
Journal
Molecular cancer research : MCR
ISSN: 1557-3125
Titre abrégé: Mol Cancer Res
Pays: United States
ID NLM: 101150042
Informations de publication
Date de publication:
03 01 2023
03 01 2023
Historique:
received:
06
06
2022
revised:
30
07
2022
accepted:
15
09
2022
pubmed:
21
9
2022
medline:
5
1
2023
entrez:
20
9
2022
Statut:
ppublish
Résumé
The most common somatic event in primary prostate cancer is a fusion between the androgen-related TMPRSS2 gene and the ERG oncogene. Tumors with these fusions, which occur early in carcinogenesis, have a distinctive etiology. A smaller subset of other tumors harbor fusions between TMPRSS2 and members of the ETS transcription factor family other than ERG. To assess the genomic similarity of tumors with non-ERG ETS fusions and those with fusions involving ERG, this study derived a transcriptomic signature of non-ERG ETS fusions and assessed this signature and ERG-related gene expression in 1,050 men with primary prostate cancer from three independent population-based and hospital-based studies. Although non-ERG ETS fusions involving ETV1, ETV4, ETV5, or FLI1 were individually rare, they jointly accounted for one in seven prostate tumors. Genes differentially regulated between non-ERG ETS tumors and tumors without ETS fusions showed similar differential expression when ERG tumors and tumors without ETS fusions were compared (differences explained: R2 = 69-77%), including ETS-related androgen receptor (AR) target genes. Differences appeared to result from similarities among ETS tumors rather than similarities among non-ETS tumors. Gene sets associated with ERG fusions were consistent with gene sets associated with non-ERG ETS fusions, including fatty acid and amino acid metabolism, an observation that was robust across cohorts. Considering ETS fusions jointly may be useful for etiologic studies on prostate cancer, given that the transcriptome is profoundly impacted by ERG and non-ERG ETS fusions in a largely similar fashion, most notably genes regulating metabolic pathways.
Identifiants
pubmed: 36125519
pii: 709264
doi: 10.1158/1541-7786.MCR-22-0446
pmc: PMC9812892
mid: NIHMS1838547
doi:
Substances chimiques
Oncogene Proteins, Fusion
0
Proto-Oncogene Proteins c-ets
0
Transcriptional Regulator ERG
0
ERG protein, human
0
TMPRSS2 protein, human
EC 3.4.21.-
Serine Endopeptidases
EC 3.4.21.-
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
14-23Subventions
Organisme : NCI NIH HHS
ID : P50 CA090381
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA167552
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA136578
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA141298
Pays : United States
Informations de copyright
©2022 American Association for Cancer Research.
Références
Br J Cancer. 2016 Apr 12;114(8):939-44
pubmed: 26986253
Annu Rev Biochem. 2011;80:437-71
pubmed: 21548782
Proc Natl Acad Sci U S A. 2020 Apr 14;117(15):8584-8592
pubmed: 32220959
Eur Urol. 2019 Jul;76(1):33-40
pubmed: 30301696
BMC Cancer. 2020 May 18;20(1):437
pubmed: 32423389
Am J Epidemiol. 2015 May 1;181(9):706-13
pubmed: 25852077
Prostate Cancer Prostatic Dis. 2019 May;22(2):292-302
pubmed: 30367117
Cancer Epidemiol Biomarkers Prev. 2016 May;25(5):745-9
pubmed: 26941365
JAMA. 2012 Nov 14;308(18):1871-80
pubmed: 23162860
Bioinformatics. 2014 Nov 1;30(21):3062-9
pubmed: 25061068
J Natl Cancer Inst. 2008 Jun 4;100(11):815-25
pubmed: 18505969
Appl Immunohistochem Mol Morphol. 2014 Sep;22(8):e32-40
pubmed: 25203299
PLoS One. 2016 Jan 05;11(1):e0146189
pubmed: 26731672
Nat Genet. 2009 May;41(5):619-24
pubmed: 19396168
Cancer Res. 2022 Aug 16;82(16):2848-2859
pubmed: 35731919
Cancer Epidemiol Biomarkers Prev. 2012 Sep;21(9):1497-509
pubmed: 22736790
Clin Cancer Res. 2017 Jan 1;23(1):81-87
pubmed: 27663590
J Biol Chem. 1997 Dec 5;272(49):30822-7
pubmed: 9388225
Nat Rev Cancer. 2017 Jun;17(6):337-351
pubmed: 28450705
J Urol. 2016 Nov;196(5):1436-1444
pubmed: 27238617
Int J Cancer. 2007 Oct 1;121(7):1571-8
pubmed: 17450530
Int J Cancer. 2020 May 15;146(10):2694-2702
pubmed: 31318977
Cancer Epidemiol Biomarkers Prev. 2018 Feb;27(2):193-200
pubmed: 29167279
Oncotarget. 2016 Jul 5;7(27):42071-42085
pubmed: 27276682
Bioinformatics. 2011 Jun 15;27(12):1739-40
pubmed: 21546393
Cancer Discov. 2014 Nov;4(11):1310-25
pubmed: 25122198
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Genes Dev. 2013 Mar 15;27(6):683-98
pubmed: 23512661
Hum Mol Genet. 2016 Dec 15;25(24):5490-5499
pubmed: 27798103
J Natl Cancer Inst. 2015 Nov 27;108(2):
pubmed: 26615022
Adv Exp Med Biol. 2019;1210:409-436
pubmed: 31900919
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
Cancer Cell. 2006 Oct;10(4):321-30
pubmed: 17010675
Eur Urol. 2016 Jan;69(1):157-65
pubmed: 26058959
Am J Epidemiol. 2017 Dec 15;186(12):1352-1361
pubmed: 28633309
Eur Urol. 2015 Oct;68(4):555-67
pubmed: 25964175
N Engl J Med. 1996 May 2;334(18):1145-9
pubmed: 8602179
J Mol Diagn. 2017 May;19(3):475-484
pubmed: 28341589
Neoplasia. 2012 Jul;14(7):600-11
pubmed: 22904677
J Mol Diagn. 2015 Jul;17(4):374-81
pubmed: 25937617
Cell. 2015 Nov 5;163(4):1011-25
pubmed: 26544944
J Natl Cancer Inst. 2013 Dec 18;105(24):1881-90
pubmed: 24292212
Oncotarget. 2016 Jan 12;7(2):1421-38
pubmed: 26623558
Cancer Epidemiol Biomarkers Prev. 2014 Oct;23(10):2027-31
pubmed: 24925673
Cancer Res. 2021 Oct 1;81(19):4981-4993
pubmed: 34362796
Cancer Cell. 2010 May 18;17(5):443-54
pubmed: 20478527
Adv Cancer Res. 2013;119:1-61
pubmed: 23870508
Prostate Cancer Prostatic Dis. 2022 Sep;25(3):397-402
pubmed: 34475523
Nucleic Acids Res. 2012 Sep 1;40(17):e133
pubmed: 22638577
Cancer Res. 2016 Apr 1;76(7):1869-81
pubmed: 26880803