Comprehensive molecular comparison of BRCA1 hypermethylated and BRCA1 mutated triple negative breast cancers.
Adult
Aged
B7-H1 Antigen
/ genetics
BRCA1 Protein
/ deficiency
Cohort Studies
DNA Methylation
/ genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Middle Aged
Mutation
/ genetics
Phenotype
Prognosis
Promoter Regions, Genetic
Transcription, Genetic
Treatment Outcome
Triple Negative Breast Neoplasms
/ blood
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 07 2020
27 07 2020
Historique:
received:
20
02
2020
accepted:
02
07
2020
entrez:
29
7
2020
pubmed:
29
7
2020
medline:
9
9
2020
Statut:
epublish
Résumé
Homologous recombination deficiency (HRD) is a defining characteristic in BRCA-deficient breast tumors caused by genetic or epigenetic alterations in key pathway genes. We investigated the frequency of BRCA1 promoter hypermethylation in 237 triple-negative breast cancers (TNBCs) from a population-based study using reported whole genome and RNA sequencing data, complemented with analyses of genetic, epigenetic, transcriptomic and immune infiltration phenotypes. We demonstrate that BRCA1 promoter hypermethylation is twice as frequent as BRCA1 pathogenic variants in early-stage TNBC and that hypermethylated and mutated cases have similarly improved prognosis after adjuvant chemotherapy. BRCA1 hypermethylation confers an HRD, immune cell type, genome-wide DNA methylation, and transcriptional phenotype similar to TNBC tumors with BRCA1-inactivating variants, and it can be observed in matched peripheral blood of patients with tumor hypermethylation. Hypermethylation may be an early event in tumor development that progress along a common pathway with BRCA1-mutated disease, representing a promising DNA-based biomarker for early-stage TNBC.
Identifiants
pubmed: 32719340
doi: 10.1038/s41467-020-17537-2
pii: 10.1038/s41467-020-17537-2
pmc: PMC7385112
doi:
Substances chimiques
B7-H1 Antigen
0
BRCA1 Protein
0
BRCA1 protein, human
0
CD274 protein, human
0
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3747Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : Wellcome Trust
ID : WT100183MA
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C60100/A25274
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C60100/A23916
Pays : United Kingdom
Références
Nature. 2012 Jan 18;481(7381):287-94
pubmed: 22258607
Cell Stress. 2019 Mar 22;3(4):118-135
pubmed: 31225507
Clin Cancer Res. 2017 Dec 15;23(24):7521-7530
pubmed: 29246904
J Clin Oncol. 2019 Mar 1;37(7):559-569
pubmed: 30650045
N Engl J Med. 2010 Nov 11;363(20):1938-48
pubmed: 21067385
Hum Pathol. 2015 Feb;46(2):182-90
pubmed: 25522926
Nat Genet. 2017 Oct;49(10):1476-1486
pubmed: 28825726
Nat Biotechnol. 2019 Jul;37(7):773-782
pubmed: 31061481
Cancer Inform. 2012;11:147-56
pubmed: 22872785
N Engl J Med. 2018 Nov 29;379(22):2108-2121
pubmed: 30345906
J Clin Oncol. 2007 May 20;25(15):2127-32
pubmed: 17513820
Ann Intern Med. 2018 Mar 6;168(5):326-334
pubmed: 29335712
J Cancer Ther Res. 2014 Mar 19;3(2):1-11
pubmed: 25177489
Oncologist. 2016 Sep;21(9):1050-62
pubmed: 27401886
J Clin Oncol. 2016 Feb 20;34(6):611-35
pubmed: 26644543
Breast Cancer Res Treat. 2015 Apr;150(3):479-86
pubmed: 25783183
Clin Cancer Res. 2019 Sep 1;25(17):5301-5314
pubmed: 31175093
Clin Cancer Res. 2016 Aug 1;22(15):3764-73
pubmed: 26957554
Cancer Res. 2012 Aug 15;72(16):4028-36
pubmed: 22706203
Nature. 2005 Apr 14;434(7035):917-21
pubmed: 15829967
Nat Genet. 2008 Jan;40(1):102-7
pubmed: 18066063
Br J Surg. 2018 Jan;105(2):e158-e168
pubmed: 29341157
Genome Med. 2015 Feb 02;7(1):20
pubmed: 25722745
Nat Med. 2019 Oct;25(10):1526-1533
pubmed: 31570822
Oncogene. 2012 Mar 1;31(9):1196-206
pubmed: 21785460
Cancers (Basel). 2020 Mar 30;12(4):
pubmed: 32235500
Nature. 2016 May 02;534(7605):47-54
pubmed: 27135926
Nat Med. 2018 May;24(5):628-637
pubmed: 29713086
Int J Cancer. 2020 Mar 1;146(5):1293-1298
pubmed: 31469414
Cancers (Basel). 2019 Jan 09;11(1):
pubmed: 30634417
Nat Biotechnol. 2015 Nov;33(11):1152-8
pubmed: 26372948
JCO Precis Oncol. 2018 Mar 09;2:
pubmed: 32913985
Oncoimmunology. 2018 Sep 11;7(12):e1509820
pubmed: 30524905
Clin Epigenetics. 2016 Nov 14;8:115
pubmed: 27895805
Ann Oncol. 2009 Dec;20(12):1913-27
pubmed: 19901010
N Engl J Med. 2019 Dec 19;381(25):2416-2428
pubmed: 31851799
J Natl Cancer Inst. 2014 Dec 04;107(1):357
pubmed: 25479802
JAMA. 2011 Oct 12;306(14):1557-65
pubmed: 21990299
J Clin Oncol. 2009 Mar 10;27(8):1160-7
pubmed: 19204204
Ann Oncol. 2018 Mar 1;29(3):654-660
pubmed: 29293876
Oncotarget. 2017 Aug 3;8(50):87151-87162
pubmed: 29152070
Clin Breast Cancer. 2015 Dec;15(6):498-504
pubmed: 26195437
Clin Epigenetics. 2018 Jul 26;10(1):99
pubmed: 30049288
BMC Bioinformatics. 2017 Feb 13;18(1):105
pubmed: 28193155
Clin Breast Cancer. 2015 Feb;15(1):80-5
pubmed: 25445419
BMC Bioinformatics. 2010 Nov 30;11:587
pubmed: 21118553
Clin Cancer Res. 2017 Jun 1;23(11):2617-2629
pubmed: 28572256
J Clin Oncol. 2015 Jun 10;33(17):1902-9
pubmed: 25847936
Ann Oncol. 2013 Jun;24(6):1498-505
pubmed: 23406733
JCO Precis Oncol. 2017 Nov;1:1-13
pubmed: 35172494
BMC Bioinformatics. 2019 May 22;20(1):264
pubmed: 31117948
Genome Biol. 2014 Aug 28;15(8):431
pubmed: 25164602
Breast Cancer Res Treat. 2018 Feb;167(3):803-814
pubmed: 29116469
Breast Cancer Res Treat. 2018 Apr;168(3):625-630
pubmed: 29275435
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
pubmed: 11309499
Sci Transl Med. 2017 Jun 7;9(393):
pubmed: 28592566
Genome Biol. 2017 Nov 15;18(1):220
pubmed: 29141660
Cancer Lett. 2019 May 28;450:88-97
pubmed: 30797818
Nature. 2012 Apr 18;486(7403):346-52
pubmed: 22522925
PLoS Med. 2016 Dec 13;13(12):e1002193
pubmed: 27959926
Nat Med. 2017 Apr;23(4):517-525
pubmed: 28288110
Ann Oncol. 2016 Aug;27(8):1532-8
pubmed: 27194814
J Clin Invest. 2011 Jul;121(7):2750-67
pubmed: 21633166