Genetics and Pathogenesis of follicular lymphoma

Specific aims: To identify genetic subtypes of follicular lymphoma (FL) based on shared genomic abnormalities and to uncover therapeutic vulnerabilities based on tumor genetics. Relevance: FL is a clinically and genetically heterogeneous disease and still considered to be incurable. Genomic sequencing studies in FL have focused on recurrent mutations in individual genes, revealing oncogenic mechanisms. We hypothesized that a nosology of FL based on shared genetic pathogenesis could aid in our understanding of treatment response and identify therapeutic vulnerabilities. Herein, we uncovered genetic subtypes of FL with distinct genotypic, epigenetic, and clinical characteristics through whole-genome integrative analysis. The genetic features of the newly characterized subsets, their mutational signatures, and the temporal ordering of identified alterations provide new insights into FL pathogenesis. The coordinate genetic signatures also predict outcome and suggest precision-medicine strategies in FL.