Biologically Distinct Breast Cancer Subtypes: The Role of Epigenetics

« Dynamic myocardial CT perfusion imaging for evaluation of myocardial ischemia as determined by MR imaging | DSCT.com – Your Dual-source CT experts

Reprogramming Normal Cell Lines into Stem-like Cells »

Biologically Distinct Breast Cancer Subtypes: The Role of Epigenetics

December 15, 2014 by 2012pharmaceutical

Biologically Distinct Breast Cancer Subtypes: The Role of Epigenetics

Reporter: Aviva Lev-Ari, PhD, RN

Article reference

A DNA methylation-based definition of biologically distinct breast cancer subtypes. Stefansson OA, Moran S, Gomez A, Sayols S, Arribas-Jorba C, Sandoval J, Hilmarsdottir H, Ólafsdóttir I, Tryggvadottir L, Jonasson JG, Eyfjord J, Esteller M. Molecular Oncology, PII: S1574-7891 (14) 00261 -0, 2014.

Mol Oncol. 2014 Nov 5. pii: S1574-7891(14)00261-0. doi: 10.1016/j.molonc.2014.10.012. [Epub ahead of print]

A DNA methylation-based definition of biologically distinct breast cancer subtypes.

Stefansson OA¹, Moran S¹, Gomez A¹, Sayols S¹, Arribas-Jorba C¹, Sandoval J¹, Hilmarsdottir H², Olafsdottir E³, Tryggvadottir L³, Jonasson JG⁴,Eyfjord J², Esteller M⁵.

Author information

Abstract

In cancer, epigenetic states are deregulated and thought to be of significance in cancer development and progression. We explored DNA methylation-based signatures in association with breast cancer subtypes to assess their impact on clinical presentation and patient prognosis. DNA methylation was analyzed using Infinium 450K arrays in 40 tumors and 17 normal breast samples, together with DNA copy number changes and subtype-specific markers by tissue microarrays. The identified methylation signatures were validated against a cohort of 212 tumors annotated for breast cancer subtypes by the PAM50 method (The Cancer Genome Atlas). Selected markers were pyrosequenced in an independent validation cohort of 310 tumors and analyzed with respect to survival, clinical stage and grade. The results demonstrate that DNA methylation patterns linked to the luminal-B subtype are characterized by CpG island promoter methylation events. In contrast, a large fraction of basal-like tumors are characterized by hypomethylation events occurring within the gene body. Based on these hallmark signatures, we defined two DNA methylation-based subtypes, Epi-LumB and Epi-Basal, and show that they are associated with unfavorable clinical parameters and reduced survival. Our data show that distinct mechanisms leading to changes in CpG methylation states are operative in different breast cancer subtypes. Importantly, we show that a few selected proxy markers can be used to detect the distinct DNA methylation-based subtypes thereby providing valuable information on disease prognosis.

NEW BREAST CANCER CLASSIFICATION BASED ON EPIGENETICS.

Posted on December 11, 2014 by Healthinnovations Leave a comment

SOURCE

http://health-innovations.org/2014/12/11/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

Date: 10/12/2014

New breast cancer classification based on epigenetics

Breast cancer is the most common in women. One in nine will suffer breast cancer over their lifetime. 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 tumor by surgery or whether if she 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.

The director of the Program Epigenetics and Cancer Biology (PEBC) at Bellvitge Biomedical Research Instiute (IDIBELL), Professor of Genetics at the University of Barcelona and ICREA researcher, Manel Esteller, has established the epigenetic patterns of breast cancer and also its clinical consequences. The finding is published in the journal Molecular Oncology.

“We’ve analyzed epigenetic alterations, namely the chemical signal called DNA methylation in 500 breast tumors and have compared the patterns obtained with the clinical behavior of these cancers,” says Esteller.

Two new subtypes of breast cancer

“We note that there are two subgroups of breast tumors by epigenome: one which we have called Epi-Basal, characterized by loss of epigenetic marks causing breakage of chromosomes and the other that we have called Epi-Luminal B, that presents epigenetic inactivation of genes that should protect us from cancer and these altered cells can no longer do it”.

The researcher highlights that “the subtype Epi-Luminal B behaves particularly aggressive form, and is associated with reduced survival of patients. This can be useful to recommend that these tumors do not be conformed to surgery and determine that it will probably be necessary to administer adjuvant chemotherapy in other words, in those tumors with a more ‘benign’ epigenetic pattern; surgery alone may be curative, thus avoiding the side effects of chemotherapy, “concludes the researcher.

Article reference

A DNA methylation-based definition of biologically distinct breast cancer subtypes. Stefansson OA, Moran S, Gomez A, Sayols S, Arribas-Jorba C, Sandoval J, Hilmarsdottir H, Ólafsdóttir I, Tryggvadottir L, Jonasson JG, Eyfjord J, Esteller M. Molecular Oncology, PII: S1574-7891 (14) 00261 -0, 2014.

http://www.idibell.cat/modul/news/en/743/new-breast-cancer-classification-based-on-epigenetics