Aplicación de la secuenciación masiva en el diagnóstico y manejo del linfoma folicular

Zusammenfassung

Follicular lymphoma (LF) is the second most common non-Hodgkin’s lymphoma, with very heterogeneous clinical and molecular features. Although it is characterized by a generally indolent clinical course, at least 20-30% of patients do not respond or progress during the first 2 years after treatment, presenting a special poor prognosis. However, there are no tools to predict the prognosis of patients at diagnosis, which is necessary to adjust their management and treatment according to their risk. The aim of this study was to analyze the genetic profile of patients with LF to identify clinical and prognostic correlations, studying the differences according on the treatment administered. To this end, genetic mutations in 64 LF-related genes were analyzed by next generation sequencing on a series of 109 patients from 3 national hospitals. All patients included in the study presented mutations related to the disease, showing a predominance of alterations in the epigenetic and transcriptional signaling pathways, with a high heterogeneity of alterations involved in other pathways, without detecting patterns or coexistences that identify subgroups. Genes with recurrent specific alterations showed a more definite prognostic impact. Patients with STAT6 Asp419 mutations had a poor prognosis and those with the CTSSTyr132Asp mutation showed much better survival and no bone marrow involvement, with potential implications for management and treatment. Patients with mutations in the ARID1A gene and those with mutations in the genes encoding mTORC1 complex proteins showed better survival in cases under rituximab-bendamustine therapy, so the detection of these alterations at the diagnosis of LF could be relevant in the choice of treatment.