Posts Tagged ‘Elias Campo’

Thursday November 17th, 2016

Clinic-IDIBAPS researchers identify that the epigenetic history of lymphoma predicts its clinical course

A study published in the journal Cancer Cell  deciphers for the first time the epigenome of mantle cell lymphoma, an aggressive type of cancer derived from B lymphocytes, the cells of the immune system responsible for producing antibodies. The research reveals in detail the epigenetic history of lymphoma. On the one hand, it identifies the cell of origin and, on the other, it reveals that the more the epigenome of tumor cells evolves, the more aggressive the patient’s clinical course is. In addition, researchers discover that three-dimensional DNA conformation changes in lymphomas and leads to the activation of cancer genes. Dr. Iñaki Martín-Subero has coordinated the study. He is researcher at the University of Barcelona and at the Molecular Mechanisms of Lymphoid Neoplasms IDIBAPS research group, led by Dr. Elías Campo.

Mantle cell lymphoma is considered a clinically aggressive type of lymphoma. However, there are some patients in whom the disease manifests mildly while in others it is very aggressive and has a fatal outcome. The causes of this clinical complexity are little known. Researchers have dissected the role of epigenetics in this type of lymphoma and have not only accurately described the evolutionary history of each patient, but also propose a new strategy to predict the aggressiveness of the disease based on its degree of epigenetic evolution.

Among the different epigenetic mechanisms, DNA methylation defines cellular identity and prints the evolutionary history of cells in DNA. Through the study of DNA methylation, researchers have analyzed in depth the mechanisms that influence the aggressiveness of lymphoma and have discovered two key factors: its origin and degree of evolution. Lymphomas that are derived from immature B lymphocytes are more aggressive than those evolving from mature B lymphocytes. However, according to Dr. Iñaki Martín-Subero, “in our study, the most important factor to explain the clinical aggressiveness is the degree of evolution of the tumor from its cell of origin. It seems that those tumors that have evolved a lot become stronger and their prognosis is adverse”.

Beyond DNA methylation

The same researchers published an article in Nature Genetics last year, in which they proposed that only a proportion of changes in the degree of methylation in tumor cells are related to cancer itself. In this work, researchers have gone one step further and, through the simultaneous study of several epigenetic mechanisms, have brought to light which are the altered regions that play a key role in cancer.

To understand it, Dr. Martin-Subero explains that, “we can imagine the epigenome as an orchestra playing a melody. The melody is the end result, the expression of the genes, and the different musicians of the orchestra are the different epigenetic mechanisms. You cannot understand the melody without knowing what each musician is doing. In this study we have analyzed each of the musicians of the epigenetic orchestra to understand how the melody changes in lymphoma“.

Of the thousands of regions in which DNA methylation changes in lymphomas, only a small proportion modify their function and, therefore, may be directly associated with tumor development. Dr. Elías Campo, an international expert on lymphomas, says that “identifying the regions that change their function in lymphoma will allow us to think about the development of more precise treatments that target those molecular alterations that transform normal cells into tumor cells“.

Changes in the three-dimensional structure of DNA in lymphomas

Among the regions with key epigenetic changes in lymphoma development, researchers focused on a particular gene, SOX11. A few years ago Dr. Campo’s group discovered that the SOX11 gene was altered in the most aggressive mantle cell lymphomas. “In 2010, we discovered that activation of the SOX11 gene is important in the development of lymphoma, but the cause of such activation has been a riddle during all these years“, explains Dr. Campo. The key to deciphering this puzzle is the integration of several epigenetic marks with the three-dimensional structure of DNA. “By studying the epigenome in patients with activated SOX11, we identified a region far from the gene that had high levels of activation. When analyzing the three-dimensional structure of this distant region, we observed that the DNA folded placing this region above the SOX11 gene, activating it“, explains Dr. Martin-Subero. “This study underscores the importance of integrating epigenetic layers to better understand molecular alterations in this type of lymphoma, and paves the way for similar studies in other cancers“, he concludes.

This study is part of the European Union-funded Blueprint project, which is part of the International Human Epigenome Consortium (IHEC). With an investment of 30 million euros, the Blueprint project is responsible for generating at least 100 reference epigenomes from the blood cells of healthy people and with different associated diseases like leukemias, lymphomas or autoimmune diseases. The team of Drs. Martín-Subero and Campo is responsible for generating the epigenome of B lymphocytes and various types of cancers derived from this cell type, including mantle cell lymphoma.

The International Consortium of the Human Epigenome

In 2003, scientists completed the Human Genome Project, which sequenced our genetic material for the first time. This milestone in the history of science gave rise to several additional projects, one of them being the Human Epigenome Project. If the genome sequence defines the personal identity, the epigenome defines the cellular identity. Therefore, each of us has a genome, but we have hundreds of epigenomes in our bodies, as many different cell types. In addition, the epigenome is not stable, can change with age, environmental exposures and also changes widely in the context of diseases such as cancer. Therefore, the Human Epigenome Project is an international challenge of great caliber and complexity.

On November 17, 2016, the International Human Epigenome Consortium (IHEC) publishes 42 articles that have sequenced the epigenome of various cell types and diseases. These articles represent the work of several groups that compose the IHEC, which are developed in Germany, Canada, South Korea, the United States, Japan, Singapore and the European Union.

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Tuesday June 14th, 2016

Andreu Mas-Colell encourages researchers from IDIBAPS to apply for a grant from the European Research Council

Professor at the University Pompeu Fabra (UPF), Andreu Mas-Colell, encourages researchers from IDIBAPS to “apply for an European Research Council (ERC) grant given the high scientific level in this institution”. Professor Mas-Colell made these remarks during the inaugural conference of the celebrations of the 20th anniversary of IDIBAPS on Monday 30th May.

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Friday June 10th, 2016

Dr. Elías Campo, awarded with the 2016 Rey Jaime I prize in the Medical Research category

Dr. Elías Campo, Research Director at Hospital Clínic, head of the Human and experimental functional oncomorphology team at IDIBAPS and Chair at the Faculty of Medicine and Health Sciences of the University of Barcelona (UB), has been awarded with the “Rey Jaime I” award in the “medical research” category. Last Tuesday the list of winners of the 2016 edition of the awards was announced in an official ceremony held at the Palace of the Generalitat Valenciana, with the presence of the board chairman, Ximo Puig; the president of the Valencian Foundation for Advanced Studies and Vice President of the Rey Jaime I” Awards Foundation, Vicente Boluda, and the Permanent Secretary of the “Rey Jaime I” Awards, Santiago Grisolía.

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Wednesday July 22nd, 2015

Mutations in the dark side of the genome cause leukemia

A study, published today in the journal Nature, marks a milestone in the understanding of chronic lymphocytic leukemia, the most common leukemia in adults, as the genomes of normal and tumor cells for more than 500 patients have been sequenced providing novel mechanisms involved in the development of this tumor. Cancer originates due to the progressive accumulation of mutations in the genome of normal cells. This is why seven years ago the International Cancer Genome Consortium (ICGC) was established. The main aim of this consortium was to sequence the genome of tumor cells from at least 500 patients, and do it for each of the 50 most frequent types of cancer in the world. The Spanish-led consortium in charge of the chronic lymphocytic leukemia study has been the first team to accomplish this ambitious objective. In this work, led by Dr. Carlos Lopez-Otin, from the University of Oviedo and by Dr. Elias Campo, from Hospital Clinic, IDIBAPS and University of Barcelona, more than 60 researchers from different centers have collaborated to mine the three billion bases of each tumor genome in search of alterations responsible for the development of this disease.

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Friday June 12th, 2015

Dr. Elías Campo recieves the Eugenio Rodriguez Pascual Award for his contributions to diagnosis and cancer therapy

Dr. Elias Campo, Research Director of the Hospital Clinic of Barcelona, Head of the Human and experimental functional oncomorphology IDIBAPS team and full professor of anatomical pathology at the University of Barcelona (UB), has been recieved the Eugenio Rodriguez Pascual Award for his contributions to diagnosis and cancer therapy. In particular, for his research about mantle cell lymphoma and laryngeal cancer. The award was presented by the Minister of Health, Social Services and Equality, Alfonso Alonso, in a ceremony held last June 10th at the Casino de Madrid.

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Monday June 8th, 2015

An epigenetic study identifies a connection between cell longevity and cancer

Researchers from IDIBAPS and the University of Barcelona (UB) lead a study, published today in the prestigious journal Nature Genetics, which reveals an unexpected connection between epigenetic changes associated with lymphocytes’ maturation and those observed in cancer. Both processes share similar changes in large regions of the genome. The work, led by Dr. Iñaki Martín-Subero, researcher in the Pathology, Pharmacology and Microbiology Department at UB and IDIBAPS, is the first in analyze the epigenome during cell maturation of B lymphocytes, the immune system cells responsible of the antibodies production, and provides epigenetic maps of each step in this process.

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