DNA methylation landscape of triple-negative ductal carcinoma in situ (DCIS) progressing to the invasive stage in canine breast cancer

• Published in: Scientific reports Vol. 10; no. 1; p. 2415
• Main Authors: Beetch, Megan, Harandi-Zadeh, Sadaf, Yang, Tony, Boycott, Cayla, Chen, Yihang, Stefanska, Barbara, Mohammed, Sulma I
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 12.02.2020; Nature Publishing Group UK
• Subjects: Animals; Apoptosis; Breast cancer; Carcinoma, Intraductal, Noninfiltrating - genetics; Carcinoma, Intraductal, Noninfiltrating - pathology; Carcinoma, Intraductal, Noninfiltrating - veterinary; Cell adhesion & migration; Cell migration; Deoxyribonucleic acid; Disease Progression; DNA; DNA Methylation; Dog Diseases - genetics; Dog Diseases - pathology; Dogs - genetics; Female; Gene expression; Gene Expression Regulation, Neoplastic; Gene regulation; Hyperplasia; Mastectomy; Signal transduction; Transcription; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - pathology; Triple Negative Breast Neoplasms - veterinary
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-59260-4

Triple-negative breast cancer (TNBC) is a subtype of breast cancer unresponsive to traditional receptor-targeted treatments, leading to a disproportionate number of deaths. Invasive breast cancer is believed to evolve from non-invasive ductal carcinoma in situ (DCIS). Detection of triple-negative DCIS (TN-DCIS) is challenging, therefore strategies to study molecular events governing progression of pre-invasive TN-DCIS to invasive TNBC are needed. Here, we study a canine TN-DCIS progression and investigate the DNA methylation landscape of normal breast tissue, atypical ductal hyperplasia (ADH), DCIS and invasive breast cancer. We report hypo- and hypermethylation of genes within functional categories related to cancer such as transcriptional regulation, apoptosis, signal transduction, and cell migration. DNA methylation changes associated with cancer-related genes become more pronounced at invasive breast cancer stage. Importantly, we identify invasive-only and DCIS-specific DNA methylation alterations that could potentially determine which lesions progress to invasive cancer and which could remain as pre-invasive DCIS. Changes in DNA methylation during TN-DCIS progression in this canine model correspond with gene expression patterns in human breast tissues. This study provides evidence for utilizing methylation status of gene candidates to define late-stage (DCIS and invasive), invasive stage only or DCIS stage only of TN-DCIS progression.