New Approaches for Breast Tumor Diagnostics: Epigenetic Profiles

The power of epigenetic-based diagnostics and prognostics is exponentially growing with expanding medical research.
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A challenge to personalized health care is the hurdle we face to understand why people are so different even though all our genes are so similar. We know single base-pair mutations in genes can be extremely important in determining health in some diseases, but we now know that gene mutations cannot account for the large degree of physiological diversity we observe between people in terms of their wellness, disease risks, response to medicines and life-expectancy.

A new field of research has exploded over the last decade termed epigenetics. This research focuses on a layer of chemical modifications that can be attached to the DNA sequence of genes. These chemical layers, the epigenome, have been known for over 50 years, but it hasn't been until recently that we've begun to realize how important this chemical layer is for normal gene function and regulation.

The recognition that this epigenome is functionally important in normal healthy tissues has opened up new avenues of research as if we've discovered another whole new genome in ourselves to explore and understand. This new layer of cellular control information in each of us is highly variable between individuals and even within one individual can vary during the course of their life. This new epigenome information provides a high-resolution profile of how and why we can be so different from each other.

The power of profiling and understanding the epigenome is evident in a recent study of breast tumors in "triple negative" women (Stirzaker et al., 2015). In terms of genetics, "triple negative" means that these women tested negative for three standard breast cancer profiling diagnostic tests (looking for mutations in estrogen and growth factor receptor genes) and yet they still developed aggressive tumors. Stirzaker's team was able to identify specific patterns of epigenetic DNA methylation associated with the tumors in comparison to paired normal control samples and more importantly, was able to discern methylation patterns associated with the prognosis for recovery and therapeutic response in these women.

The goal of personalized diagnostics is based on the realization that often "one size" test does not fit all. Because of our inherent molecular and physiological differences, the efficacy of any diagnostic test can be increased by optimizing the test strategy for specific groups of different people. In the above case, standard breast cancer risk tests were ineffective for these triple-negative women because their tumors developed differently. Better diagnostics lead to earlier detection and better tailoring of intervention strategies and therapeutics. This is called stratification: don't lump all people into the same test and don't attack all tumors with the same treatment.

There are several recent medical studies indicating how epigenetic profiling of breast tumors may explain and predict how and why different women develop different types of breast tumors. These tumors are variable in their growth rates, response to therapeutics and invasiveness. Epigenetics is beginning to provide a quantifiable measure of how to differentiate these patient risk groups and tumor types.

The power of epigenetic-based diagnostics and prognostics is exponentially growing with expanding medical research. In the PubMed literature database maintained by the NIH's National Center for Biotechnology Information, there were 2,576 medical research papers published on epigenetics in 2014, compared to just 103 published 10 years ago in 2004. The epigenome represents a sensitive and highly-individualized source of personalized genetic information that we are just beginning to understand and utilize for better health care and wellness management.


Stirzaker et al. (2015)."Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value." Nature Communications 6:5899, doi:10.1038/ncomms6899