DNA methylation profiling reveals a predominant immune component in breast cancers.
Bottom Line: Understanding this diversity is essential to improving diagnosis and optimizing treatment.By means of DNA methylation profiling of 248 breast tissues, we have highlighted the existence of previously unrecognized breast cancer groups that go beyond the currently known 'expression subtypes'.Further, we highlighted a set of immune genes having high prognostic value in specific tumour categories.
Affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.Show MeSH
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Mentions: We next sought to refine the methylation-based taxonomy of our tumour set. As shown in Fig 3A, the unsupervised analysis of recurrent methylation patterns yielded six distinct entities (clusters 1 to 6; see Fig S5 and Supplemental Materials and Methods Section of Supporting Information for the formal procedure for cluster definition). We then wished to relate these methylation clusters with the known breast cancer ‘expression subtypes’. Currently, on the basis of gene expression profiles, four subtypes are distinguished (see also Introduction): basal-like, HER2-positive, luminal A and luminal B breast cancers (Sotiriou & Piccart, 2007). IHC and gene expression profiling (Fig 3A) revealed a significant preponderance of HER2-positive tumours in cluster 2, basal-like tumours in cluster 3, and luminal A tumours in cluster 6. Interestingly, no single ‘expression subtype’ appeared to dominate in methylation clusters 1, 4 and 5: cluster 1 contained HER2, basal-like as well as luminal B tumours; cluster 4 appeared to be a mix of HER2 and luminal B tumours; and cluster 5 contained both luminal A and B tumours (Fig 3A; see also Table SX and Fig S6 of Supporting Information). Hence, this importantly demonstrates the potential of DNA methylation profiling to refine breast cancer classification.
Affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.