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Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis.

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 + /luminal subtype had lower fibroblast and endothelial content, while triple-negative breast cancer/basal metastases showed a decrease in B and T cells. In 17% of metastases, DNA hypermethylation and/or focal deletions were identified near HLA-A and were associated with reduced expression and lower immune cell infiltrat

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Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis.

> 商业许可源文 · EUROPE_PMC · [CC-BY](https://creativecommons.org/licenses/by/)

书目信息

  • 引用：Garcia-Recio S, Hinoue T, Wheeler GL, Kelly BJ, Garrido-Castro AC, Pascual T, De Cubas AA, Xia Y, Felsheim BM, McClure MB, Rajkovic A, Karaesmen E, Smith MA, Fan C, Ericsson PIG, Sanders ME, Creighton CJ, Bowen J, Leraas K, Burns RT, Coppens S, Wheless A, Rezk S, Garrett AL, Parker JS, Foy KK, Shen H, Park BH, Krop I, Anders C, Gastier-Foster J, Rimawi MF, Nanda R, Lin NU, Isaacs C, Marcom PK, Storniolo AM, Couch FJ, Chandran U, Davis M, Silverstein J, Ropelewski A, Liu MC, Hilsenbeck SG, Norton L, Richardson AL, Symmans WF, Wolff AC, Davidson NE, Carey LA, Lee AV, Balko JM, Hoadley KA, Laird PW, Mardis ER, King TA, AURORA US Network, Perou CM. (2023). Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis. Nature cancer. PMID 36585450 · PMC9886551 · DOI 10.1038/s43018-022-00491-x
  • 证据类型：PRIMARY_RESEARCH
  • 主题：multi-omics
  • 被引次数（采集时）：140
  • 原始记录：[Europe PMC](https://europepmc.org/article/MED/36585450)
  • 来源许可：[CC-BY](https://creativecommons.org/licenses/by/)

    • 作者摘要（按来源许可复用）

    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 + /luminal subtype had lower fibroblast and endothelial content, while triple-negative breast cancer/basal metastases showed a decrease in B and T cells. In 17% of metastases, DNA hypermethylation and/or focal deletions were identified near HLA-A and were associated with reduced expression and lower immune cell infiltrates, especially in brain and liver metastases. These findings could have implications for treating individuals with metastatic breast cancer with immune- and HER2-targeting therapies.

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    Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis. · GeniOmics