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DNA methylation profiling reveals a predominant immune component in breast cancers.

Dedeurwaerder S, Desmedt C, Calonne E, Singhal SK, Haibe-Kains B, Defrance M, Michiels S, Volkmar M, Deplus R, Luciani J, Lallemand F, Larsimont D, Toussaint J, Haussy S, Rothé F, Rouas G, Metzger O, Majjaj S, Saini K, Putmans P, Hames G, van Baren N, Coulie PG, Piccart M, Sotiriou C, Fuks F - EMBO Mol Med (2011)

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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.

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Complexity and heterogeneity of breast cancers as revealed by DNA methylation: a meaningful basis for refining breast tumour taxonomyDNA methylation profiling of the main set identifies six groups of tumours, termed clusters 1–6, displaying differences in terms of ‘expression subtype composition’ and clinical characteristics (see also Fig S6 and Table SX of Supporting Information).Comparison of the methylation group assigned to each tumour of the main set by the unsupervised cluster analysis and the 86 CpG-classifier established by the nearest centroid classification method (Lusa et al, 2007; Sorlie et al, 2003; see also Fig S8 and Table SXIV of Supporting Information).Classification of each tumour of the validation set into one of the six methylation groups by means of the 86 CpG-classifier (see also Fig S9 and Table SXVI of Supporting Information). Note that the 6 groups obtained for the validation set presented the same ‘expression subtype composition’ and clinical characteristics as the groups obtained for the main set (see also Fig S10 and Table SXVII of Supporting Information).
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fig03: Complexity and heterogeneity of breast cancers as revealed by DNA methylation: a meaningful basis for refining breast tumour taxonomyDNA methylation profiling of the main set identifies six groups of tumours, termed clusters 1–6, displaying differences in terms of ‘expression subtype composition’ and clinical characteristics (see also Fig S6 and Table SX of Supporting Information).Comparison of the methylation group assigned to each tumour of the main set by the unsupervised cluster analysis and the 86 CpG-classifier established by the nearest centroid classification method (Lusa et al, 2007; Sorlie et al, 2003; see also Fig S8 and Table SXIV of Supporting Information).Classification of each tumour of the validation set into one of the six methylation groups by means of the 86 CpG-classifier (see also Fig S9 and Table SXVI of Supporting Information). Note that the 6 groups obtained for the validation set presented the same ‘expression subtype composition’ and clinical characteristics as the groups obtained for the main set (see also Fig S10 and Table SXVII of Supporting Information).

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.


DNA methylation profiling reveals a predominant immune component in breast cancers.

Dedeurwaerder S, Desmedt C, Calonne E, Singhal SK, Haibe-Kains B, Defrance M, Michiels S, Volkmar M, Deplus R, Luciani J, Lallemand F, Larsimont D, Toussaint J, Haussy S, Rothé F, Rouas G, Metzger O, Majjaj S, Saini K, Putmans P, Hames G, van Baren N, Coulie PG, Piccart M, Sotiriou C, Fuks F - EMBO Mol Med (2011)

Complexity and heterogeneity of breast cancers as revealed by DNA methylation: a meaningful basis for refining breast tumour taxonomyDNA methylation profiling of the main set identifies six groups of tumours, termed clusters 1–6, displaying differences in terms of ‘expression subtype composition’ and clinical characteristics (see also Fig S6 and Table SX of Supporting Information).Comparison of the methylation group assigned to each tumour of the main set by the unsupervised cluster analysis and the 86 CpG-classifier established by the nearest centroid classification method (Lusa et al, 2007; Sorlie et al, 2003; see also Fig S8 and Table SXIV of Supporting Information).Classification of each tumour of the validation set into one of the six methylation groups by means of the 86 CpG-classifier (see also Fig S9 and Table SXVI of Supporting Information). Note that the 6 groups obtained for the validation set presented the same ‘expression subtype composition’ and clinical characteristics as the groups obtained for the main set (see also Fig S10 and Table SXVII of Supporting Information).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3377115&req=5

fig03: Complexity and heterogeneity of breast cancers as revealed by DNA methylation: a meaningful basis for refining breast tumour taxonomyDNA methylation profiling of the main set identifies six groups of tumours, termed clusters 1–6, displaying differences in terms of ‘expression subtype composition’ and clinical characteristics (see also Fig S6 and Table SX of Supporting Information).Comparison of the methylation group assigned to each tumour of the main set by the unsupervised cluster analysis and the 86 CpG-classifier established by the nearest centroid classification method (Lusa et al, 2007; Sorlie et al, 2003; see also Fig S8 and Table SXIV of Supporting Information).Classification of each tumour of the validation set into one of the six methylation groups by means of the 86 CpG-classifier (see also Fig S9 and Table SXVI of Supporting Information). Note that the 6 groups obtained for the validation set presented the same ‘expression subtype composition’ and clinical characteristics as the groups obtained for the main set (see also Fig S10 and Table SXVII of Supporting Information).
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.

Show MeSH
Related in: MedlinePlus