Epigenomic and Transcriptomic Characterization of Secondary Breast Cancers.

Publication Title

Annals of surgical oncology : the official journal of the Society of Surgical Oncology

Authors

Amanda N Graff-Baker, Center for Endocrine Tumors and Disorders, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA.Follow
Javier I Orozco, Center for Endocrine Tumors and Disorders, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA.Follow
Diego M Marzese, Center for Endocrine Tumors and Disorders, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA.Follow
Matthew P Salomon, Center for Endocrine Tumors and Disorders, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA.Follow
Dave S B Hoon, Center for Endocrine Tumors and Disorders, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA.Follow
Melanie Goldfarb, Center for Endocrine Tumors and Disorders, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA.Follow

Document Type

Article

Publication Date

6-28-2018

Abstract

BACKGROUND: Molecular alterations impact tumor prognosis and response to treatment. This study was designed to identify transcriptomic and epigenomic signatures of breast cancer (BC) tumors from patients with any prior malignancy.

METHODS: RNA-sequencing and genome-wide DNA methylation profiles from BCs were generated in the Cancer Genome Atlas project. Patients with secondary breast cancer (SBC) were separated by histological subtype and matched to primary breast cancer controls to create two independent cohorts of invasive ductal (IDC, n = 36) and invasive lobular (ILC, n = 40) carcinoma. Differentially expressed genes, as well as differentially methylated genomic regions, were integrated to identify epigenetically regulated abnormal gene pathways in SBCs.

RESULTS: Differentially expressed genes were identified in IDC SBCs (n = 727) and in ILC SBCs (n = 261; Wilcoxon's test; P < 0.05). In IDC SBCs, 105 genes were upregulated and hypomethylated, including an estrogen receptor gene, and 73 genes were downregulated and hypermethylated, including genes involved in antigen presentation and interferon response pathways (HLA-E, IRF8, and RELA). In ILC SBCs, however, only 17 genes were synchronously hypomethylated and upregulated, whereas 46 genes hypermethylated and downregulated. Interestingly, the SBC gene expression signatures closely corresponded with each histological subtype with only 1.51% of genes overlapping between the two histological subtypes.

CONCLUSIONS: Differential gene expression and DNA methylation signatures are seen in both IDC and ILC SBCs, including genes that are relevant to tumor growth and proliferation. Differences in gene expression signatures corresponding with each histological subtype emphasize the importance of disease subtype-specific evaluations of molecular alterations.

Clinical Institute

Cancer

Specialty/Research Institute

Oncology