Genetic diversity of newly diagnosed follicular lymphoma

Abstract

Follicular lymphoma (FL) is the second most common form of non-Hodgkin lymphoma (NHL) and often follows an indolent disease course with slow progression.1, 2 However, patients may develop resistant disease; in addition, transformation to a more aggressive subtype of lymphoma occurs at a rate of 2–3% per year.3, 4, 5, 6 FL arises from germinal center B cells and the most common molecular defect is t(14;18)(q32;q21) in 85–90% of the cases, which results in the IGH-BCL2 fusion gene and the overexpression of the anti-apoptotic oncogene BCL2.7 However, the t(14;18) is also observed in healthy individuals and FL patients who are in long-term remission2 suggesting the existence of additional genomic alternations that impact disease course. Recently, massive parallel exome or whole genome sequencing of FL tumors and follow-up validation studies have discovered that point mutations in genes involved in epigenetic regulation and chromatin modification, including MLL2, EZH2, CREBBP, EP300 and MEF2B, dominate the FL landscape.8, 9, 10, 11, 12 Mutations in JAK-STAT pathway genes and B-cell receptor (BCR)/NF-κB signaling genes have also been identified, but with lower frequencies.11