Catalan scientists participate in international consortium to decode part of human epigenome

Researchers from Hospital Clinic–IDIBAPS, CNAG, Barcelona Supercomputing Center (BSC), Center for Genomic Regulation (CRG) and Idibell are participating in the International Human Epigenome Consortium (IHEC) to shed light on the epigenetic mechanisms behind some of the most prevalent diseases, like cancer and diabetes. The project has just published 42 articles simultaneously in a variety of prestigious science journals.

The team at Hospital Clinic–IDIBAPS, coordinated by Dr. Iñaki Martín-Subero and led by Dr. Elías Campo, published a study in the journal Cancer Cell that decodes the epigenome of mantle cell lymphoma, an aggressive type of cancer derived from B lymphocytes (the cells in the immune system that produce antibodies).

First of all, the research has identified the cell the lymphomas come from and concludes that those derived from immature B lymphocytes are more aggressive than those from mature B lymphocytes. Furthermore, it reveals that the more the epigenome of the tumor cells evolves, the more aggressive it becomes.

The researchers analyzed the mechanisms that influence the aggressiveness of the lymphoma because in some patients it is quite mild and in others, very aggressive. Based on their results, they have also proposed a new strategy to predict its aggressiveness based on its epigenetic evolution.

Through this work, researchers have identified which mutated regions play a key role in this cancer by simultaneously studying different epigenetic mechanisms. “Identifying the regions with a different function in the lymphoma will allow us to think about developing more precise treatments,” explains Dr. Elías Campo, international expert in lymphomas.

Map of DNA methylation patterns

The study led by CNAG-CRG, published in the journal Cell Reports, created a map of DNA methylation, one of the epigenetic mechanisms that drives cells to develop different cell identities.

The researchers, led by Roderic Guigó (from the CRG Bioinformatics and Genomics program), analyzed global development of DNA methylation patterns in healthy and diseased cells, discovering that cancerous cells lose control of DNA methylation. Better understanding the epigenetic changes that occur in the presence or absence of a disease will help better treat, prevent and prognosticate many diseases in a much more personalized way. The breakthroughs, however, are still far from clinical practice.

These two studies led by Catalan scientists are part of the Blueprint project, which channels all IHEC studies in the European Union and has received €30 millions in funding. The project is charged with generating at least 100 reference epigenomes from the blood cells of healthy individuals and people with associated diseases, like types of leukemia, lymphomas and autoimmune diseases.

International Human Epigenome Consortium

The International Human Epigenome Consortium is a project of the Human Genome Project, which first sequenced all of our genetic material. It is made up of members from Germany, Canada, South Korea, the United States, Japan, Singapore and the European Union.

While the genome defines our personal identity, the epigenome defines cell identity –so each of us have hundreds of epigenomes in our body. The epigenome isn’t permanent; it can change with age, environmental exposure and disease. One of the great unsolved mysteries of biology is why cells with the same DNA end up becoming one type or another. The epigenome determines which molecular switches make a cell mutate and how.

Exhaustive analysis of the epigenomes of normal and abnormal cells will allow for new methods of diagnosing and treating a variety of diseases. This project is a highly complex international challenge that involves analyzing millions of data sets and hundreds of scientists around the world will spend decades working on it.

Related publications:

• Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage. Cancer Cell (14 November 2016) doi: http://dx.doi.org/10.1016/j.ccell.2016.09.014
• Distinct Trends of DNA Methylation Patterning in the Innate and Adaptive Immune Systems. Cell Reports (15 November 2016) doi: 10.1016/j.celrep.2016.10.054