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tumours, methylation, genes, expression, cancer, breast, prc, gene, pubmed, basallike, subtypes, article, cells, lumb, google, scholar, levels, targets, data, methylated, cell, figure, luminal, cpg, cas, molecular, set, relative, found, dna, analysis, subtype, target, ezh, file, patterns, tumour, central, cpgs, sites, additional, low, luma, cluster, samples, results, average, identified, status, calculated,

Topics {✒️}

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         headline:Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns
         description:Five different molecular subtypes of breast cancer have been identified through gene expression profiling. Each subtype has a characteristic expression pattern suggested to partly depend on cellular origin. We aimed to investigate whether the molecular subtypes also display distinct methylation profiles. We analysed methylation status of 807 cancer-related genes in 189 fresh frozen primary breast tumours and four normal breast tissue samples using an array-based methylation assay. Unsupervised analysis revealed three groups of breast cancer with characteristic methylation patterns. The three groups were associated with the luminal A, luminal B and basal-like molecular subtypes of breast cancer, respectively, whereas cancers of the HER2-enriched and normal-like subtypes were distributed among the three groups. The methylation frequencies were significantly different between subtypes, with luminal B and basal-like tumours being most and least frequently methylated, respectively. Moreover, targets of the polycomb repressor complex in breast cancer and embryonic stem cells were more methylated in luminal B tumours than in other tumours. BRCA2-mutated tumours had a particularly high degree of methylation. Finally, by utilizing gene expression data, we observed that a large fraction of genes reported as having subtype-specific expression patterns might be regulated through methylation. We have found that breast cancers of the basal-like, luminal A and luminal B molecular subtypes harbour specific methylation profiles. Our results suggest that methylation may play an important role in the development of breast cancers.
         datePublished:2010-06-18T00:00:00Z
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            Molecular Subtype
            Methylation Frequency
            Luminal Tumour
            Luminal Progenitor
            Embryonic Ectoderm Development
            Cancer Research
            Oncology
            Surgical Oncology
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      headline:Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns
      description:Five different molecular subtypes of breast cancer have been identified through gene expression profiling. Each subtype has a characteristic expression pattern suggested to partly depend on cellular origin. We aimed to investigate whether the molecular subtypes also display distinct methylation profiles. We analysed methylation status of 807 cancer-related genes in 189 fresh frozen primary breast tumours and four normal breast tissue samples using an array-based methylation assay. Unsupervised analysis revealed three groups of breast cancer with characteristic methylation patterns. The three groups were associated with the luminal A, luminal B and basal-like molecular subtypes of breast cancer, respectively, whereas cancers of the HER2-enriched and normal-like subtypes were distributed among the three groups. The methylation frequencies were significantly different between subtypes, with luminal B and basal-like tumours being most and least frequently methylated, respectively. Moreover, targets of the polycomb repressor complex in breast cancer and embryonic stem cells were more methylated in luminal B tumours than in other tumours. BRCA2-mutated tumours had a particularly high degree of methylation. Finally, by utilizing gene expression data, we observed that a large fraction of genes reported as having subtype-specific expression patterns might be regulated through methylation. We have found that breast cancers of the basal-like, luminal A and luminal B molecular subtypes harbour specific methylation profiles. Our results suggest that methylation may play an important role in the development of breast cancers.
      datePublished:2010-06-18T00:00:00Z
      dateModified:2010-06-18T00:00:00Z
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      pageEnd:16
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         Molecular Subtype
         Methylation Frequency
         Luminal Tumour
         Luminal Progenitor
         Embryonic Ectoderm Development
         Cancer Research
         Oncology
         Surgical Oncology
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      name:Markus Ringnér
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      name:Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
      name:CREATE Health Strategic Centre for Translational Cancer Research, Lund University, Lund, Sweden
      name:Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
      name:CREATE Health Strategic Centre for Translational Cancer Research, Lund University, Lund, Sweden
      name:Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
      name:CREATE Health Strategic Centre for Translational Cancer Research, Lund University, Lund, Sweden
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      name:Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
      name:CREATE Health Strategic Centre for Translational Cancer Research, Lund University, Lund, Sweden
      name:Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden
      name:Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
      name:CREATE Health Strategic Centre for Translational Cancer Research, Lund University, Lund, Sweden

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