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Is epigenomics the next breakthrough in precision medicine?

In the past few decades, the field of genomics has rapidly evolved. From the Human Genome Project to the Million Genomes Project, molecular insight into our own DNA has never been more attainable. These new insights can let us know when we might have cancer-causing alterations in our genes. Personal genomics tests may promise to integrate our unique genetic makeup into clinical decision making. However, there is more to our genome than what such tests can reveal. In addition to the DNA code, there is a hidden layer of regulation controlling the activity of genes. Have you thought about why identical twins can still be different? How it is possible that the lifestyle of our grandparents can affect our lives today? The hidden layer responsible for fine-tuning alongside our DNA is called epigenetics.

Epigenetics makes sense of chemical modifications that influence gene expression without altering the DNA sequence. In fact, our own cells use epigenetic chemical regulators to control gene activity. For example, environmental influences such as nutrition or cigarette smoke, as well as our own hormones, can have a strong epigenetic impact on how active our genes are.

Epigenomics, an approach to studying epigenetic effects, thus holds a lot of promise for cancer treatments. However, there are a number of questions that need to be answered first. We need to understand how the epigenome of a healthy person looks, and if it changes as we age. From there, we can see how the epigenome of a sick person might differ. In the future, these important questions will be addressed by personalized epigenomics, which tries to extract information out of a comprehensive picture of a person’s epigenome.

“There is a hidden layer of regulation controlling the activity of genes”

You may ask: why can we not create a simple test that tells us if we have good genes but an unfavorable epigenome? Our epigenome is highly dynamic. Recently, the systems biology and cancer metabolism lab at UC Merced published discoveries about an epigenetic factor called “Jumonji”. This factor can affect how an entire network of cancer genes behaves, and takes on the role of a cancer gene to bring uncontrollable cell growth. Epigenomic regulators, including Jumonji, remove or add chemical marks allowing for transient gene read-outs while blocking it in the next minute. If such important regulators are mistuned and do not put the right marks on their target genes, altered metabolism triggers unlimited cellular growth and cancer can arise.

Is it too early for consumers to think about personalized tests? Is the information still too cryptic or too unreliable to draw conclusions?

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High-throughput screening in combination with systems biology analysis identifies epigenomic master regulators in malignant melanoma. Photo by Systems Biology and Cancer Metabolism Laboratory, Fabian V. Filipp. Used with permission. CC BY-NC-SA.

Personal gene tests for cancer exist but often do not take epigenetic factors into account. Actor Ben Stiller claims a simple genetic test for abnormally high levels of the prostate antigen saved his life. Abnormally high levels of the prostate specific antigen (PSA) in the blood can mean that a man has prostate cancer, but not always. This has led to substantial overdiagnosis of prostate tumors in the past and has resulted in much debate about whether PSA screenings are recommended.

Drugs that target the epigenome raise optimism as a viable direction of clinical research. It remains open to debate, however, whether epigenetics is a beneficial force since epigenetics was found in some cases to actually assist the cancer cells in manipulating the immune system and to evade the drug targeting approaches. Researchers have compared this delicate epigenetic homeostasis to Yin and Yang. Complementary forces keep each other in check but if one force overtakes the system, it is out of equilibrium. For the cells, this can mean unlimited growth, cancer, or death. The goal in precision medicine then, is to acquire a thorough understanding of epigenetic regulation so that drugs can be designed to counter-regulate these factors.

As seen in recent breakthroughs in melanoma research, a genetic mutation of an epigenetic player allowed for a drug to be created to stop the ability of cancer cells to hide from the immune system thus making the tumor vulnerable. For cancer patients with epigenetic activation, epigenetic drugs promise hope.

Featured image credit: Precision targeting and big data in cancer medicine. High-throughput screen of malignant melanoma cells using genomics, epigenomics, and metabolomics. Image by Systems Biology and Cancer Metabolism Laboratory, Fabian V. Filipp. Used with permission. CC BY-NC-SA.

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