Tumor suppressors in follicular lymphoma

Follicular lymphoma (FL) is the most common indolent lymphoma. The vast majority of cases are associated with the chromosome translocation t(14;18), a somatic rearrangement that leads to constitutive expression of the anti-apoptotic BCL2 protein. Although t(14;18) clearly represents an important early event in FL pathogenesis, abundant evidence indicates that it is not sufficient. In particular, the recent application of next-generation DNA sequencing technology has uncovered numerous recurrent somatic genomic alterations associated with FL, most of which affect tumor suppressor genes (TSGs). In this article we review the existing literature on TSGs involved in the development and progression of FL. We consider the genes that are most frequently targeted by deleterious mutation, deletion or epigenetic silencing, along with strategies for developing new treatments that exploit the susceptibilities that may be conferred on lymphoma cells by the loss of particular TSGs.