Genetics of Transformed Follicular Lymphoma

Abstract

Histological transformation (HT) to a more aggressive disease–mostly diffuse large B-cell lymphoma–is considered one of the most dismal events in the clinical course of follicular lymphoma (FL). Current knowledge has not found a single biological event specific for HT, although different studies have highlighted common genetic alterations, such as TP53 and CDKN2A/B loss, and MYC translocations, among others. Together, they increase genomic complexity and mutational burden at HT. A better knowledge of HT pathogenesis would presumably help to find diagnostic biomarkers allowing the identification of patients at high-risk of transformation, as well as the discrimination from patients with FL recurrence, and those who remain in remission. This would also help to identify new drug targets and the design of clinical trials for the treatment of transformation. In the present review we provide a comprehensive overview of the genetic events frequently identified in transformed FL contributing to the switch towards aggressive behaviour, and we will discuss current open questions in the field of HT.