Discovered that key genes to stop the development of lymphomas acquire mutations in the sites that regulate the 'splicing signals'

Research from the University of Granada has identified new mutations related to lymphoma that help to better understand how these tumors are produced. The study, in which the Biosanitary Research Institute of Granada (ibs.GRANADA) and the Pfizer-University of Granada-Junta de Andalucía Center for Genomics and Oncology Research (Genyo) have participated, has been carried out by the team of the professor at the UGR Pedro Medina Vico, from the Department of Biochemistry and Molecular Biology I, and its first authors were the researchers Álvaro Andrades Delgado and Juan Carlos Álvarez Pérez.

Lymphoma is a type of cancer that affects cells of the immune system called lymphocytes. Unlike leukemias, which are also produced by tumors in blood cells, lymphomas generate solid tumors that manifest in the lymphatic system. According to the Spanish Society of Medical Oncology, in 2021 more than ten thousand new cases of lymphoma were diagnosed in Spain, with diffuse large B-cell lymphoma (DLBCL) being the most frequent subtype and one of those with the worst prognosis. DLBCL can affect people of any age, but it usually occurs in older people. DLBCL is one of the most aggressive lymphomas with the worst prognosis. About 35-45% of patients do not survive five years after their diagnosis.

Researchers from Professor Medina's group have analyzed genetic data from more than XNUMX DLBCL patients, searching for new mutations that may be related to the disease. Thanks to this, they have managed to observe that, until now, the accumulations of mutations in specific regions of DNA called “splicing signals” had gone unnoticed and that they were present in important genes that slow down the development of lymphoma.

“Human genes have information stored in a somewhat particular way. This is due to the fact that they encode the information in a fragmented way, since there are regions that should not be read and must be cut and eliminated so that a suitable product can be generated. If these cuts and splices of information are not carried out precisely, functional products will not be created”, comments Professor Medina.

"Thus, in this work we have discovered that mutations accumulate that prevent a correct cut and splice from being generated when important genes are read to stop the development of lymphomas", adds Pedro Medina. The finding is relevant from a clinical point of view, because some of the genes identified by the authors (such as CD79B) have gained special importance in recent years, since their mutations have been proposed for the molecular diagnosis of lymphomas. In addition, these mutations may be related to the patient's response to standard therapy, and their relationship with the response to new, state-of-the-art experimental treatments is being studied. For this reason, it is especially important to identify all the molecular alterations related to DLBCL in order, in the future, to have more precise and personalized methods to diagnose and choose the most effective treatment for each patient.

Bibliographic reference: Andrades Delgado, Alvaro, Juan Carlos Álvarez-Pérez, Juan Rodrigo Patiño-Mercau, Marta Cuadros, Carlos Baliñas-Gavira, and Pedro P Medina. "Recurrent splice site mutations affect key diffuse large B-cell lymphoma genes". Blood, January 5, 2022, blood.2021011708. https://doi.org/10.1182/blood.2021011708