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New breast cancer classification based on epigenetics.

Researchers from Institut d’Investigació Biomèdica de Bellvitge (IDIBELL) have established the epigenetic patterns of breast cancer and also its clinical consequences. The opensource study is published in the journal Molecular Oncology.

Statistics from The Breast Cancer Research Foundation state that nearly 1.7 million new breast cancer cases were diagnosed in 2012.  Breast cancer is the second most common cancer in women and men worldwide. In 2012, it represented about 12 percent of all new cancer cases and 25 percent of all cancers in women.  Breast cancer is the most frequently diagnosed cancer among women in 140 of 184 countries worldwide.

Globally, breast cancer now represents one in four of all cancers in women.  Progress in prevention and early detection, and the use of chemotherapy after surgery (adjuvant chemotherapy), have achieved significantly increase survival in this disease in the last ten years, but much remains to be done.

The identification of patients with high-risk breast cancer is key to knowing whether a patient will require only the removal of the tumour by surgery or whether if they will need additional chemotherapy to make sure the removal of breast cancer cells. Currently, known genetic mutations and expression patterns are determined, but the puzzle of the genetics of the disease remains a large unfinished part.

To address this the researchers analyzed epigenetic alterations, namely the chemical signal called DNA methylation in 500 breast tumours and have compared the patterns obtained with the clinical behaviour of these cancers.

The team note that there are two subgroups of breast tumours by epigenome; one which they have named Epi-Basal, characterized by loss of epigenetic marks causing breakage of chromosomes and the other that the researchers have called Epi-Luminal B, that presents epigenetic inactivation of genes that should protect humans from cancer and the altered cells that can no longer do it.

The researchers highlight that the subtype Epi-Luminal B behaves particularly aggressive form, and is associated with reduced survival of patients. They would therefore recommend that with this class of tumour the medical team avoid surgery and instead administer adjuvant chemotherapy and in those tumours with a more ‘benign’ epigenetic pattern; surgery alone may be curative, thus avoiding the side effects of chemotherapy.

Source:  Institut d’Investigació Biomèdica de Bellvitge

DNA methylation changes in breast tumors are non-random and define patterns correlated with clinically and biologically relevant subtypes. A) Cluster analysis of differentially methylated CpGs between breast cancers and normal breast tissue (the top 5000 most significant CpGs). Tumor characteristics (by columns on top of the heat-map) in terms of breast cancer subtype along with the presence of acquired mutations in the TP53 gene are displayed together with the CpG context (by rows on the left-hand side) according to the color scheme shown at the right-hand side and bottom of the figure, respectively. The statistically significant tumor patterns/clusters (identified by the pvclust method in R) are shown as colored bars immediately below the dendrogram. B) The top 10 significant CpG's specifically characterizing each of the four “core” subtypes are shown, i.e. the LumA, LumB, HER2 and Basal-like subtypes. Note, 5NP (i.e. unclassified tumors due to negativity for all five phenotypic markers, i.e. ER, PR, HER2, CK5/6 and EGFR) and breast tumors with unknown subtype information are grouped together as 5NP/NA and were not included in this analysis. The normal breast tissue samples are shown and indicated in black on top of the heat-map. Note, the heat-map colors reflect beta-values representing the degree of methylation from low to high as green to red, respectively (wherein black represents heterogenous/hemi-methylation), as shown on the scale at the top-right hand side of the figure.  A DNA methylation-based definition of biologically distinct breast cancer subtypes.  Esteller et al 2014.
DNA methylation changes in breast tumors are non-random and define patterns correlated with clinically and biologically relevant subtypes. A) Cluster analysis of differentially methylated CpGs between breast cancers and normal breast tissue (the top 5000 most significant CpGs). Tumor characteristics (by columns on top of the heat-map) in terms of breast cancer subtype along with the presence of acquired mutations in the TP53 gene are displayed together with the CpG context (by rows on the left-hand side) according to the color scheme shown at the right-hand side and bottom of the figure, respectively. The statistically significant tumor patterns/clusters (identified by the pvclust method in R) are shown as colored bars immediately below the dendrogram. B) The top 10 significant CpG’s specifically characterizing each of the four “core” subtypes are shown, i.e. the LumA, LumB, HER2 and Basal-like subtypes. Note, 5NP (i.e. unclassified tumors due to negativity for all five phenotypic markers, i.e. ER, PR, HER2, CK5/6 and EGFR) and breast tumors with unknown subtype information are grouped together as 5NP/NA and were not included in this analysis. The normal breast tissue samples are shown and indicated in black on top of the heat-map. Note, the heat-map colors reflect beta-values representing the degree of methylation from low to high as green to red, respectively (wherein black represents heterogenous/hemi-methylation), as shown on the scale at the top-right hand side of the figure. A DNA methylation-based definition of biologically distinct breast cancer subtypes. Esteller et al 2014.

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One thought on “New breast cancer classification based on epigenetics. Leave a comment

  1. My research, summarised in ‘Trace element nutrition’ and other material accessible by searching DOCSTOC using ‘michaeltdeans’, demonstrates that selenium deficiency is the main cause of breast cancer. Following a chance observation as a Cambridge undergraduate leading to a consistent model for the origin of life, 47 years’ study has confirmed its consequences in many fields.

    ‘Transport DNAs’ and ‘differentiation DNAs’, analogues of tRNAs and mRNAs, control membrane transport. Water transport is mediated by phosphomevalonate derived from saturated fats and its lactone. The pituitary gland delivers Se in vasopressin, vitamin E converts it to selenite, carrier for manganese, catalysing cholesterol synthesis from mevalonate.

    There’s a strong correlation between surface geology and breast cancer incidence, veterinary studies afford ample supporting evidence. My work describes life before protein synthesis evolved, its watermark persists throughout the biosphere. Your collaboration in verifying and publishing my work would be welcome.

    Yours sincerely,

    Michael T Deans MA Cantab MSc Lond

    4 Cavendish House, Cavendish Road, Chiswick, London W4 3TD

    T: 020 89956525, E: michaeltdeans@gmail.com, W: http://www.scienceuncoiled.co.uk

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