DNA hypomethylation silences anti-tumor immune genes in early prostate cancer and CTCs.

Animals Humans Male Mice Carcinogenesis / genetics DNA DNA Methylation Epigenesis, Genetic Prostatic Neoplasms / genetics Neoplastic Cells, Circulating
CD1A DNA hypomethylation IFI16 NKT cells circulating tumor cells immune surveillance lipid antigens prostate cancer single-cell sequencing tumorigenesis

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
22 06 2023
Historique:
received: 19 07 2022
revised: 09 02 2023
accepted: 17 05 2023
medline: 26 6 2023
pubmed: 17 6 2023
entrez: 16 6 2023
Statut: ppublish

Résumé

Cancer is characterized by hypomethylation-associated silencing of large chromatin domains, whose contribution to tumorigenesis is uncertain. Through high-resolution genome-wide single-cell DNA methylation sequencing, we identify 40 core domains that are uniformly hypomethylated from the earliest detectable stages of prostate malignancy through metastatic circulating tumor cells (CTCs). Nested among these repressive domains are smaller loci with preserved methylation that escape silencing and are enriched for cell proliferation genes. Transcriptionally silenced genes within the core hypomethylated domains are enriched for immune-related genes; prominent among these is a single gene cluster harboring all five CD1 genes that present lipid antigens to NKT cells and four IFI16-related interferon-inducible genes implicated in innate immunity. The re-expression of CD1 or IFI16 murine orthologs in immuno-competent mice abrogates tumorigenesis, accompanied by the activation of anti-tumor immunity. Thus, early epigenetic changes may shape tumorigenesis, targeting co-located genes within defined chromosomal loci. Hypomethylation domains are detectable in blood specimens enriched for CTCs.

Identifiants

DOI: 10.1016/j.cell.2023.05.028 PMID: 37327786 PMC: PMC10436379
pubmed: 37327786
pii: S0092-8674(23)00580-9
doi: 10.1016/j.cell.2023.05.028
pmc: PMC10436379
mid: NIHMS1910396
pii:
doi:

Substances chimiques

DNA 9007-49-2

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

2765-2782.e28

Subventions

Organisme : NCI NIH HHS
ID : R01 CA129933
Pays : United States
Organisme : NIBIB NIH HHS
ID : U01 EB012493
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA259007
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA268933
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIBIB NIH HHS
ID : P41 EB002503
Pays : United States

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests Massachusetts General Hospital (MGH) has applied for patents regarding the CTC-iChip technology and CTC detection signatures. M.T., S.M., and D.A.H. are cofounders and have equity in Tell-Bio, which is not related to this work. The interests of these authors were reviewed and managed by MGH and Mass General Brigham (MGB) in accordance with their conflict of interest policies.

Références

Science. 2018 Nov 30;362(6418):1060-1063
pubmed: 30498128
Genome Res. 2014 Feb;24(2):177-84
pubmed: 24068705
Nat Commun. 2015 Jan 21;6:6033
pubmed: 25607992
Bioinformatics. 2015 Jan 15;31(2):166-9
pubmed: 25260700
Bioinformatics. 2016 Jan 15;32(2):289-91
pubmed: 26424858
Cancer Res. 2001 Apr 15;61(8):3225-9
pubmed: 11309270
Cancer Cell. 2002 May;1(4):299-305
pubmed: 12086841
Science. 2011 Mar 25;331(6024):1565-70
pubmed: 21436444
J Endocrinol. 2012 May;213(2):173-82
pubmed: 22393245
Science. 2009 Oct 9;326(5950):289-93
pubmed: 19815776
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Hum Mol Genet. 2011 Feb 15;20(4):670-80
pubmed: 21112978
Nat Protoc. 2014 Jan;9(1):171-81
pubmed: 24385147
Cold Spring Harb Perspect Biol. 2016 Sep 01;8(9):
pubmed: 27194046
Science. 2022 Dec 23;378(6626):1276-1277
pubmed: 36548410
Ann Oncol. 2021 Sep;32(9):1167-1177
pubmed: 34176681
Cell Res. 2016 Mar;26(3):304-19
pubmed: 26902283
Nucleic Acids Res. 2016 Jul 8;44(W1):W160-5
pubmed: 27079975
Cancers (Basel). 2020 Jul 01;12(7):
pubmed: 32630247
Nat Biotechnol. 2012 May;30(5):413-21
pubmed: 22544022
Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20111-6
pubmed: 24282295
Sci Rep. 2020 Nov 10;10(1):19453
pubmed: 33173202
Nat Rev Immunol. 2013 Feb;13(2):101-17
pubmed: 23334244
Clin Cancer Res. 2008 Jun 1;14(11):3254-61
pubmed: 18519750
Aging (Albany NY). 2019 Jul 11;11(13):4521-4535
pubmed: 31295725
Nat Methods. 2014 Aug;11(8):817-820
pubmed: 25042786
Cancer Discov. 2014 Jun;4(6):650-61
pubmed: 24801577
Cell. 2020 Sep 17;182(6):1474-1489.e23
pubmed: 32841603
Nat Protoc. 2012 Mar 01;7(3):562-78
pubmed: 22383036
J Clin Oncol. 1994 Dec;12(12):2634-9
pubmed: 7527455
Nat Methods. 2017 Apr;14(4):411-413
pubmed: 28218897
Nat Genet. 2020 Aug;52(8):778-789
pubmed: 32661416
Elife. 2019 Nov 26;8:
pubmed: 31767055
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D493-6
pubmed: 14681465
Nature. 1983 Jan 6;301(5895):89-92
pubmed: 6185846
Nat Methods. 2015 Nov;12(11):1058-60
pubmed: 26344043
Nat Protoc. 2017 Mar;12(3):534-547
pubmed: 28182018
Ann Oncol. 2020 Jun;31(6):745-759
pubmed: 33506766
PLoS One. 2011;6(6):e20702
pubmed: 21695190
Cancer Res. 1993 Sep 1;53(17):3869-73
pubmed: 7689419
Oncotarget. 2016 Oct 25;7(43):70388-70403
pubmed: 27611943
Trends Immunol. 2016 Nov;37(11):738-754
pubmed: 27623113
Biochem Pharmacol. 2014 Dec 1;92(3):405-14
pubmed: 25199457
Genome Biol. 2008;9(9):R137
pubmed: 18798982
Cancer Res. 2004 Mar 15;64(6):1975-86
pubmed: 15026333
J Biol Chem. 2004 Nov 12;279(46):48350-9
pubmed: 15339928
Am J Surg Pathol. 2016 Feb;40(2):244-52
pubmed: 26492179
Nat Genet. 2011 Nov 27;44(1):40-6
pubmed: 22120008
Nat Rev Immunol. 2004 Mar;4(3):231-7
pubmed: 15039760
Cancer Res. 2005 Dec 15;65(24):11565-71
pubmed: 16357166
Cancer Res. 2006 Nov 15;66(22):10683-90
pubmed: 17108105
Science. 2015 Sep 18;349(6254):1351-6
pubmed: 26383955
Science. 1985 Apr 12;228(4696):187-90
pubmed: 2579435
Nat Rev Immunol. 2020 Nov;20(11):651-668
pubmed: 32433532
Nat Genet. 2018 Apr;50(4):591-602
pubmed: 29610480
Cell. 2015 Nov 5;163(4):1011-25
pubmed: 26544944
Cancer Res. 2008 Nov 1;68(21):8954-67
pubmed: 18974140
Sci Transl Med. 2010 Mar 31;2(25):25ra23
pubmed: 20424012
Eur Urol. 2016 Mar;69(3):428-35
pubmed: 26166626
Am J Pathol. 2013 Dec;183(6):1960-1970
pubmed: 24113458
Bioinformatics. 2011 Jun 1;27(11):1571-2
pubmed: 21493656
Cold Spring Harb Perspect Med. 2019 May 1;9(5):
pubmed: 30201787
Nat Methods. 2017 Apr;14(4):407-410
pubmed: 28218898
Cancer Discov. 2018 Mar;8(3):288-303
pubmed: 29301747
J Neurol Sci. 2016 Oct 15;369:39-42
pubmed: 27653862
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Ann Oncol. 2018 Jun 1;29(6):1445-1453
pubmed: 29635542
Oncogene. 2002 Aug 12;21(35):5427-40
pubmed: 12154405
Nat Genet. 2011 Jun 26;43(8):768-75
pubmed: 21706001
Genome Med. 2014 Aug 26;6(8):61
pubmed: 25191524
Genome Res. 2012 Feb;22(2):246-58
pubmed: 22156296
Stem Cells. 2012 Jun;30(6):1087-96
pubmed: 22593016
Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W170-5
pubmed: 18487274
In Vitro Cell Dev Biol Anim. 1995 Jan;31(1):14-24
pubmed: 7535634
Bioinformatics. 2015 Jun 15;31(12):2032-4
pubmed: 25697820
Cancer Immunol Res. 2015 May;3(5):425-35
pubmed: 25941354
Bioinformatics. 2015 Aug 1;31(15):2595-7
pubmed: 25810428
Sci Transl Med. 2013 Apr 3;5(179):179ra47
pubmed: 23552373

Auteurs

Hongshan Guo (H)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

Joanna A Vuille (JA)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.

Ben S Wittner (BS)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.

Emily M Lachtara (EM)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.

Yu Hou (Y)

Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Maoxuan Lin (M)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Ting Zhao (T)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Ayush T Raman (AT)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Hunter C Russell (HC)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.

Brittany A Reeves (BA)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.

Haley M Pleskow (HM)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

Chin-Lee Wu (CL)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Andreas Gnirke (A)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Alexander Meissner (A)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin 14195, Germany.

Jason A Efstathiou (JA)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

Richard J Lee (RJ)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Mehmet Toner (M)

Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Center for Engineering in Medicine and Shriners Hospital for Children, Harvard Medical School, Boston, MA 02114, USA.

Martin J Aryee (MJ)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Michael S Lawrence (MS)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

David T Miyamoto (DT)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Electronic address: dmiyamoto@mgh.harvard.edu.

Shyamala Maheswaran (S)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: maheswaran@helix.mgh.harvard.edu.

Daniel A Haber (DA)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: dhaber@mgh.harvard.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › DNA hypomethylation silences anti-tumor immune...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › DNA hypomethylation silences anti-tumor immune...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › DNA hypomethylation silences anti-tumor immune...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Carcinogenèse › DNA hypomethylation silences anti-tumor immune...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › DNA hypomethylation silences anti-tumor immune...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › DNA hypomethylation silences anti-tumor immune...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › DNA hypomethylation silences anti-tumor immune...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › DNA hypomethylation silences anti-tumor immune...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Métastase tumorale › Cellules tumorales circulantes › DNA hypomethylation silences anti-tumor immune...