Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL, 20–30%) after diffuse large B-cell lymphoma (DLBCL). Despite the introduction of rituximab and the high response rate to first-line treatment, approximately 20% of the FL patients relapse or progress within 2 years of receiving first-line therapy. Therefore, the major challenge is finding biomarkers that identify high-risk patients at diagnosis.

The aim of the present study was to analyze in detail the genetic landscape and genetic complexity by next-generation sequencing (NGS), defined by the number of mutated genes, in a FL series to improve our understanding of the biology of FL and its impact on the clinical outcome of the patients. A total of 83 FL grade I–IIIA patients diagnosed at the University Hospital of Salamanca between January 2000 and December 2017 were retrospectively included.

In summary, our study has increased the knowledge of the FL biology through the characterization of the mutational landscape of a representative series of FL patients, and allowed to confirm the dependence of the tumor germinal center B-cell on alterations in genes involved in epigenetic modification, signaling, and transcription factors. 

 Keywords: Follicular lymphoma, non-Hodgkin lymphoma, high-risk patients