The genome of one of the most agressive lymphomas has been deciphered
October 21, 2013
Mantle cell lymphoma is a cancer very aggressive cancer of blood cells that is hard to treat
Mantle cell lymphoma is a very hard to treat and aggressive type of cancer that originates in blood cells and the lymphatic ganglions. In order to identify the molecular alterations responsible of this tumor and to facilitate the development of new treatments, a team of scientists led by Drs. Xose S. Puente and Carlos López-Otín of the University of Oviedo, and Drs. Silvia Beà and Elías Campo of the IDIBAPS, Hospital Clínic, University of Barcelona, has sequenced the genome of more than 30 samples of this lymphoma. The result of this work, published today by the prestigious North-American journal Proceedings of the National Academy of Sciences, presents the first genomical analysis of this disease. "This study allows us to know better the causes and evolution of this complex neoplasia, and it has identified targets for new treatments", comments Dr. Silvia Beà, first author of the study.
The authors have analyzed the genome of the tumoral cells at the start of the disease and throughout several years after the treatment at the moment of relapse. Thus, they have been able to evaluate the modifications of the genome related to the evolution of the disease. These analyses have led to the discovery of different genes involved in the progression of these lymphomas and in the generation of mechanisms of resistance to chemotherapy. Furthermore, a group of patients with a very fast evolution of the disease, presenting mutations in the NOTCH1 and NOTCH2 genes, has been identified. These mutations may be therapeutic targets because there are already some drugs that block their activity and may be used in more complex cases of mantle cell lymphoma. A group of patients with a small number of mutations in the tumor, and whose disease evolves very slowly, has also been identified. This way, the knowledge of the genome of these lymphomas may guide the selection of the most adequate treatments for each patient.
The analysis of the tumoral genome of more than 30 patients led to the idenfification of new therapeutic targets
This work has been conducted thanks to the funding of the Association for International Cancer Research (United Kingdom), the Lymphoma Research Foundation (USA) and the Health Institute Carlos III (Spain), and it illustrates how new genome sequencing technologies are revolutionizing the study and knowledge of different types of cancer. Thus, for the past three years, the Consortium for Genomic Research on Chronic Lymphatic Leukemia, of which these researchers are part, has sequenced hundreds of patients with the most common leukemia today, identifying new mechanisms of tumoral progression and new therapeutic targets. These studies have allowed them to apply the genomic studies in the clinical practice to imporve the diagnosis and treatment of cancer patients.
The figure describes the genome of a mantle lymphoma, with all the identified mutations and the distance they are placed at, which allows researchers to idenify some of the areas with an accumulation of mutations that define the hypermutated regions.