Publication Date
1-1-2023
Journal
Nature Cancer
DOI
10.1038/s43018-022-00491-x
PMID
36585450
PMCID
PMC9886551
PubMedCentral® Posted Date
12-30-2022
PubMedCentral® Full Text Version
Post-Print
Published Open-Access
yes
Keywords
Female, Animals, Humans, Multiomics, Breast, Triple Negative Breast Neoplasms, DNA Methylation, Mammary Neoplasms, Animal, Epigenesis, Genetic, Tumor Microenvironment
Abstract
The AURORA US Metastasis Project was established with the goal to identify molecular features associated with metastasis. We assayed 55 females with metastatic breast cancer (51 primary cancers and 102 metastases) by RNA sequencing, tumor/germline DNA exome and low-pass whole-genome sequencing and global DNA methylation microarrays. Expression subtype changes were observed in ~30% of samples and were coincident with DNA clonality shifts, especially involving HER2. Downregulation of estrogen receptor (ER)-mediated cell-cell adhesion genes through DNA methylation mechanisms was observed in metastases. Microenvironment differences varied according to tumor subtype; the ER
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