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Review
. 2018 Dec;23(4):223-235.
doi: 10.1007/s10911-018-9414-2. Epub 2018 Oct 10.

Beyond DNA: the Role of Epigenetics in the Premalignant Progression of Breast Cancer

Rebecca S DeVaux  1 , Jason I Herschkowitz  2
Affiliations
Review

Beyond DNA: the Role of Epigenetics in the Premalignant Progression of Breast Cancer

Rebecca S DeVaux et al. J Mammary Gland Biol Neoplasia. 2018 Dec.

Abstract

Ductal Carcinoma in Situ (DCIS) is an early breast cancer lesion that is considered a nonobligate precursor to development of invasive ductal carcinoma (IDC). Although only a small subset of DCIS lesions are predicted to progress into a breast cancer, distinguishing innocuous from minacious DCIS lesions remains a clinical challenge. Thus, patients diagnosed with DCIS will undergo surgery with the potential for radiation and hormone therapy. This has led to a current state of overdiagnosis and overtreatment. Interrogating the transcriptome alone has yet to define clear functional determinants of progression from DCIS to IDC. Epigenetic changes, critical for imprinting and tissue specific development, in the incorrect context can lead to global signaling rewiring driving pathological phenotypes. Epigenetic signaling pathways, and the molecular players that interpret and sustain their signals, are critical to understanding the underlying pathology of breast cancer progression. The types of epigenetic changes, as well as the molecular players, are expanding. In addition to DNA methylation, histone modifications, and chromatin remodeling, we must also consider enhancers as well as the growing field of noncoding RNAs. Herein we will review the epigenetic interactions that have been uncovered in early stage lesions that impact breast cancer progression, and how these players may be utilized as biomarkers to mitigate overdiagnosis and overtreatment.

Keywords: Breast cancer progression; DCIS; DNA methylation; Enhancer; Epigenetics; Histone modification; IDC; Noncoding RNA.

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Figures

Fig. 1
Fig. 1
Genes impacted by indicated epigenetic modification are listed where they are found to be dysregulated, either between normal and either atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS) or between DCIS and invasive ductal carcinoma. All genes listed under DNA methylation demonstrated an increase in methylation in indicated transition
See this image and copyright information in PMC

References

    1. Esserman LJ, Thompson IM, Jr, Reid B. Overdiagnosis and overtreatment in cancer: an opportunity for improvement. JAMA. 2013;310(8):797–8. - PubMed
    1. Breast Cancer Facts & Figures 2015–2016. American Cancer Society.
    1. Lopez-Garcia MA, et al. Breast cancer precursors revisited: molecular features and progression pathways. Histopathology. 2010;57(2):171–192. - PubMed
    1. Polyak K. Breast cancer: origins and evolution. J Clin Invest. 2007;117(11):3155–3163. - PMC - PubMed
    1. Allegra CJ, et al. NIH state-of-the-science conference statement: diagnosis and management of ductal carcinoma in situ (DCIS) NIH Consens State Sci Statements. 2009;26(2):1–27. - PubMed

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