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Invasive breast cancer is believed to evolve from non-invasive ductal carcinoma <jats:italic>in situ<\/jats:italic> (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.<\/jats:p>","DOI":"10.1038\/s41598-020-59260-4","type":"journal-article","created":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T11:03:58Z","timestamp":1581505438000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["DNA methylation landscape of triple-negative ductal carcinoma in situ (DCIS) progressing to the invasive stage in canine breast cancer"],"prefix":"10.1038","volume":"10","author":[{"given":"Megan","family":"Beetch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadaf","family":"Harandi-Zadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cayla","family":"Boycott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Stefanska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sulma I.","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,12]]},"reference":[{"key":"59260_CR1","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1016\/j.celrep.2019.06.046","volume":"28","author":"P Bouchal","year":"2019","unstructured":"Bouchal, P. et al. Breast Cancer Classification Based on Proteotypes Obtained by SWATH Mass Spectrometry. Cell Rep. 28, 832\u2013843.e837, https:\/\/doi.org\/10.1016\/j.celrep.2019.06.046 (2019).","journal-title":"Cell Rep."},{"key":"59260_CR2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-62","volume":"14","author":"LA Sturtz","year":"2014","unstructured":"Sturtz, L. A., Melley, J., Mamula, K., Shriver, C. D. & Ellsworth, R. E. Outcome disparities in African American women with triple negative breast cancer: a comparison of epidemiological and molecular factors between African American and Caucasian women with triple negative breast cancer. BMC cancer 14, 62, https:\/\/doi.org\/10.1186\/1471-2407-14-62 (2014).","journal-title":"BMC cancer"},{"key":"59260_CR3","doi-asserted-by":"publisher","first-page":"3412","DOI":"10.1002\/cncr.32207","volume":"125","author":"LC Scott","year":"2019","unstructured":"Scott, L. C., Mobley, L. R., Kuo, T. M. & Il\u2019yasova, D. 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