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The genome of a really aggressive lymphoma has been sequenced

Profile of four mantle cell lymphoma cases (six samples). Distribution of somatic alterations, each case is represented in a different color.

Profile of four mantle cell lymphoma cases (six samples). Distribution of somatic alterations, each case is represented in a different color.

22/10/2013

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Mantle cell lymphoma is one of most aggressive and difficult to treat cancers originated in blood cells and lymph nodes. To identify the molecular alterations responsible for this tumour and to facilitate the development of new treatments, a group of scientists led by Xose S. Puente and Carlos López Otín from the University of Oviedo, and researchers Sílvia Beà and Elías Campo, from the Faculty of Medicine of the UB, IDIBAPS and the Hospital Clínic of Barcelona, have sequenced the genome of more than thirty lymphomas. Results, published on the journal Proceedings of the National Academy of Sciences (PNAS), are the first comprehensive genomic analysis of the disease. “The study provides insight into causes and evolution of this complex neoplasm and has identified targets for new treatments”, explains Dr Sílvia Beà, first author of the study.
Researchers analysed the genome of tumour cells at the onset of the disease and within several years after treatment, when relapses took place. This procedure has enabled to evaluate genome alterations associated with disease progression. These analyses discovered several genes involved in the progression of lymphomas and the emergence of chemotherapy resistance mechanisms. Moreover, a group of patients who present a quick evolution of the disease and mutations in genes NOTCH1 and NOTCH2 has been defined. These mutations may be therapeutic targets because drugs which block their activity are available; these drugs may be useful in difficult cases of mantle cell lymphoma. Researchers also identified a group of patients with a small number of mutations in the tumour and slow disease progression. Thus, to know the genome of these lymphomas may help to select appropriate treatments for each patient.

The research has been possible thanks to the funds given by the Association for International Cancer Research (United Kingdom), the Lymphoma Research Foundation (USA) and the Institute of Health Carlos III (Spain); it illustrates how new genome sequencing technologies are revolutionizing the study and knowledge of several types of cancer. For the last three years, the Spanish Consortium for the Study of the Genome of the Chronic Lymphatic Leukaemia has sequenced the genome of hundreds of patients of this frequent leukaemia; researchers have identified new mechanisms of tumour progression and new targets for therapeutic intervention. These studies enable to apply genomic studies to clinical practice in order to improve cancer patients’ diagnosis and treatment.

 
 
Reference:

S. Beà, R. Valdés-Mas, A. Navarro, I. Salaverria, D. Martín-Garcia, P. Jares, E. Giné, M. Pinyol, C. Royo, F. Nadeu, L. Conde, M. Juan, G. Clot, P. Vizán, L. Di Croce, D. A. Puente, M. López-Guerra, A. Moros, G. Roue, M. Aymerich, N. Villamor, Ll. Colomo, A. Martínez, A. Valera, J. I. Martín-Subero, V. Amador, L. Hernández, M. Rozman, A. Enjuanes, P. Forcada, A. Muntañola, E. M. Hartmann, M. J. Calasanz, A. Rosenwald, G. Ott, J. M. Hernández-Rivas, W. Klapper, R. Siebert, A. Wiestner, W. H. Wilson, D. Colomer, A. López-Guillermo, C. López-Otín, X. S. Puente, and E. Campo."Landscape of somatic mutations and clonal evolution in mantle cell lymphoma". Proceedings of the National Academy of Sciences (PNAS), October  2013. doi: 10.1073/pnas.1314608110

 

 

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