Methylation marks for tracking the advance of breast cancer

Posted by Biome on 2nd September 2014 - 0 Comments


In recent years it has become increasingly clear that DNA methylation can dramatically change in tumour tissues, and also that these changes are not static – as the cancer progresses and evolves, so does the DNA methylation in these cancer cells. Previous studies in brain, gastric, colorectal and several other cancers showed that such epigenetic changes begin to occur early in tumour development and can be used as markers of disease progression. Now, in a Genome Biology study, Vessela Kristensen from the Institute for Cancer Research, Norway, and colleagues describe the DNA methylation dynamics of breast cancer.

Ductal carcinoma in situ (DCIS) is a precursor to invasive breast cancer. The authors generated DNA methylation profiles of nearly 300 breast cancer samples representing healthy breast tissue, pure DCIS, a mix of the precursor and invasive breast cancer, and later stages of the carcinoma. They find that most of the changes in methylation already occurred at the DCIS stage. Notably they also identify a set of 18 CpGs that are differentially methylated between different stages of the disease, which form a signature with prognostic value. The signature, discovered from the dataset of 176 patients, was further validated in nearly 600 other samples.

With this, and other articles published in the Genome Biology special issue on the genomics of cancer progression and heterogeneity, there is a growing trend in studies looking to identify signatures that can be used to predict prognosis and survival. Researchers are more often reaching for DNA methylation measurements, slowly replacing gene expression-based signatures.

It is perhaps the greatest testimony to this genomic modification, which has until recently been underused in this area. DNA methylation assays are easy to set up and use in a clinical setting, DNA methylation is stable over time, and also quite insensitive to laboratory handling – all of these facets makes this cellular characteristic ideally suited for clinical utilisation.

 

Written by Rafal Marszalek, Senior Assistant Editor for Genome Biology.

 

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Genome-wide DNA methylation profiles in progression to in situ and invasive carcinoma of the breast with impact on gene transcription and prognosis
Thomas Fleischer, Arnoldo Frigessi, Kevin C Johnson, Hege Edvardsen, Nizar Touleimat, Jovana Klajic, Margit LH Riis, Vilde Haakensen, Fredrik Wärnberg, Bjørn Naume, Åslaug Helland, Anne-Lise Børresen-Dale, Jörg Tost, Brock C Christensen and Vessela N Kristensen
Genome Biology 2014, 15:435

Genome Biology

 

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Genome-wide DNA methylation profiles in progression to in situ and invasive carcinoma of the breast with impact on gene transcription and prognosis

Fleischer T, Frigessi A, Johnson KC, Edvardsen H, Touleimat N, Klajic J, Riis MLH, Haakensen VD et al.
Genome Biology 2014, 15:435

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