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Comprehensive molecular comparison of BRCA1 hypermethylated and BRCA1 mutated triple negative breast cancers.

Abstract：

: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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Glodzik D,Bosch A,Hartman J,Aine M,Vallon-Christersson J,Reuterswärd C,Karlsson A,Mitra S,Niméus E,Holm K,Häkkinen J,Hegardt C,Saal LH,Larsson C,Malmberg M,Rydén L,Ehinger A,Loman N,Kvist A,Ehrencrona H,Nik-Zainal

doi

10.1038/s41467-020-17537-2

subject

Has Abstract

pub_date

2020-07-27 00:00:00

pages

3747

issue

1

issn

2041-1723

pii

10.1038/s41467-020-17537-2

journal_volume

11

pub_type

杂志文章

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