LTR retroelement expansion of the human cancer transcriptome and immunopeptidome revealed by de novo transcript assembly.
Journal
Genome research
ISSN: 1549-5469
Titre abrégé: Genome Res
Pays: United States
ID NLM: 9518021
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
26
01
2019
accepted:
21
08
2019
pubmed:
21
9
2019
medline:
20
3
2020
entrez:
21
9
2019
Statut:
ppublish
Résumé
Dysregulated endogenous retroelements (EREs) are increasingly implicated in the initiation, progression, and immune surveillance of human cancer. However, incomplete knowledge of ERE activity limits mechanistic studies. By using pan-cancer de novo transcript assembly, we uncover the extent and complexity of ERE transcription. The current assembly doubled the number of previously annotated transcripts overlapping with long-terminal repeat (LTR) elements, several thousand of which were expressed specifically in one or a few related cancer types. Exemplified in melanoma, LTR-overlapping transcripts were highly predictable, disease prognostic, and closely linked with molecularly defined subtypes. They further showed the potential to affect disease-relevant genes, as well as produce novel cancer-specific antigenic peptides. This extended view of LTR elements provides the framework for functional validation of affected genes and targets for cancer immunotherapy.
Identifiants
pubmed: 31537638
pii: gr.248922.119
doi: 10.1101/gr.248922.119
pmc: PMC6771403
doi:
Substances chimiques
Retroelements
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1578-1590Subventions
Organisme : Medical Research Council
ID : MC_U117512710
Pays : United Kingdom
Organisme : Arthritis Research UK
ID : FC001162
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_16062
Pays : United Kingdom
Organisme : Arthritis Research UK
ID : FC001099
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 102898/B/13/Z
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom
Informations de copyright
© 2019 Attig et al.; Published by Cold Spring Harbor Laboratory Press.
Références
Cell. 2018 Jul 26;174(3):549-563.e19
pubmed: 29937226
Nat Rev Cancer. 2011 Sep 23;11(10):726-34
pubmed: 21941284
Nature. 2014 Mar 27;507(7493):462-70
pubmed: 24670764
Nat Rev Immunol. 2016 Apr;16(4):207-19
pubmed: 27026073
Nat Commun. 2016 Jan 05;7:10238
pubmed: 26728094
Sci Transl Med. 2015 Jul 8;7(295):295ra109
pubmed: 26157031
Mol Cell Proteomics. 2012 Apr;11(4):M111.010587
pubmed: 22186715
JCI Insight. 2017 Feb 9;2(3):e91078
pubmed: 28194445
Nat Med. 2010 May;16(5):571-9, 1p following 579
pubmed: 20436485
Cell. 2012 May 11;149(4):740-52
pubmed: 22579280
Nat Med. 2018 Aug;24(8):1143-1150
pubmed: 30038220
J Clin Invest. 2018 Nov 1;128(11):4804-4820
pubmed: 30137025
Blood. 2016 Jan 14;127(2):221-32
pubmed: 26463425
Electrophoresis. 1999 Dec;20(18):3551-67
pubmed: 10612281
Cancer Cell. 2017 Aug 14;32(2):204-220.e15
pubmed: 28810145
Anal Chem. 2003 May 15;75(10):2470-7
pubmed: 12918992
Cell. 2015 Jan 15;160(1-2):48-61
pubmed: 25594174
Oncotarget. 2015 Nov 24;6(37):40095-111
pubmed: 26517682
Neoplasia. 2016 Aug;18(8):489-99
pubmed: 27566105
Cancer Res. 2004 Jan 15;64(2):509-16
pubmed: 14744763
Oncogene. 2014 May 22;33(21):2790-800
pubmed: 23770851
Cancer Cell. 2018 Aug 13;34(2):211-224.e6
pubmed: 30078747
Prostate. 2015 Dec;75(16):1958-71
pubmed: 26384005
Science. 2016 Mar 4;351(6277):1083-7
pubmed: 26941318
Nat Genet. 2019 Apr;51(4):611-617
pubmed: 30926969
J Clin Invest. 2008 Mar;118(3):1099-109
pubmed: 18292810
Biol Direct. 2018 Jul 16;13(1):14
pubmed: 30012197
Cell. 2015 Jun 18;161(7):1681-96
pubmed: 26091043
Front Microbiol. 2017 Dec 12;8:2489
pubmed: 29312197
Nat Rev Genet. 2012 Mar 16;13(4):283-96
pubmed: 22421730
Cancer Immunol Immunother. 2012 Jul;61(7):1093-100
pubmed: 22187063
Mob DNA. 2016 Dec 1;7:24
pubmed: 27980689
Nat Commun. 2018 Mar 2;9(1):903
pubmed: 29500430
Science. 2017 Jul 21;357(6348):
pubmed: 28729483
PLoS Genet. 2011 Dec;7(12):e1002384
pubmed: 22144907
Science. 2018 Oct 26;362(6413):
pubmed: 30361341
Semin Cancer Biol. 2010 Aug;20(4):246-53
pubmed: 20685251
Nature. 2017 Aug 24;548(7668):471-475
pubmed: 28813415
Cell. 2015 Aug 27;162(5):961-73
pubmed: 26317465
AIDS Res Hum Retroviruses. 2006 Jan;22(1):52-6
pubmed: 16438646
Nucleic Acids Res. 2019 Jan 8;47(D1):D766-D773
pubmed: 30357393
Nat Biotechnol. 2018 Dec;36(11):1056-1058
pubmed: 30114007
Cell Rep. 2018 Apr 10;23(2):512-521
pubmed: 29642008
Science. 2015 Apr 3;348(6230):69-74
pubmed: 25838375
Nature. 2001 Feb 15;409(6822):860-921
pubmed: 11237011
Nat Commun. 2016 Nov 21;7:13404
pubmed: 27869121
Sci Transl Med. 2018 Dec 5;10(470):
pubmed: 30518613
Nat Genet. 2015 Mar;47(3):199-208
pubmed: 25599403
Cancer Res. 1998 Apr 1;58(7):1515-20
pubmed: 9537257
Science. 2015 May 8;348(6235):648-60
pubmed: 25954001
J Invest Dermatol. 1970 Jul;55(1):65-70
pubmed: 5425068
Nature. 2015 Oct 15;526(7573):453-7
pubmed: 26444240
Cancer Res. 2016 Apr 15;76(8):2177-85
pubmed: 26862115
Cancer Res. 2002 Oct 1;62(19):5510-6
pubmed: 12359761
PLoS Genet. 2009 Feb;5(2):e1000383
pubmed: 19214206
Cell. 2015 Aug 27;162(5):974-86
pubmed: 26317466
Philos Trans R Soc Lond B Biol Sci. 2017 Oct 19;372(1732):null
pubmed: 28893944