Epigenomic and Transcriptomic Characterization of Secondary Breast Cancers

• Published in: Annals of surgical oncology Vol. 25; no. 10; pp. 3082 - 3087
• Main Authors: Graff-Baker, Amanda N., Orozco, Javier I. J., Marzese, Diego M., Salomon, Matthew P., Hoon, Dave S. B., Goldfarb, Melanie
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.10.2018; Springer Nature B.V
• Subjects: Aged; Antigen presentation; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Carcinoma, Ductal, Breast - genetics; Carcinoma, Ductal, Breast - pathology; Carcinoma, Ductal, Breast - surgery; Carcinoma, Lobular - genetics; Carcinoma, Lobular - pathology; Carcinoma, Lobular - surgery; DNA Methylation; DNA sequencing; Epigenomics; Female; Follow-Up Studies; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genome, Human; Genomes; Histocompatibility antigen HLA; Humans; Invasiveness; Malignancy; Medicine; Medicine & Public Health; Middle Aged; Neoplasms, Second Primary - genetics; Neoplasms, Second Primary - pathology; Neoplasms, Second Primary - surgery; Oncology; Patients; Prognosis; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; RelA protein; Ribonucleic acid; RNA; Surgery; Surgical Oncology; Transcriptome; Translational Research and Biomarkers; Tumors; Interferon Response Pathway; The Cancer Genome Atlas (TCGA); Duct Invasion (IDC); Secondary Breast Cancer (SBC); Epigenomic Signatures
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-018-6582-7

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.