Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations

Follicular lymphoma (FL) is genetically characterized by the presence of the t(14; 18)(q32;q21) chromosomal translocation in approximately 90% of cases. In contrast to FL carrying the t(14; 18), their t(14; 18)-negative counterparts are less well studied about their immunohistochemical, genetic, molecular, and clinical features. Within a previously published series of 184 FLs grades 1 to 3A with available gene expression data, we identified 17 FLs lacking the t(14; 18). Comparative genomic hybridization and high-resolution single nucleotide polymorphism (SNP) array profiling showed that gains/amplifications of the BCL2 gene locus in 18q were restricted to the t(14; 18)-positive FL subgroup. A comparison of gene expression profiles showed an enrichment of germinal center B cell-associated signatures in t(14; 18)-positive FL, whereas activated B cell-like, NF kappa B, proliferation, and bystander cell signatures were enriched in t(14; 18)-negative FL. These findings were confirmed by immunohistochemistry in an independent validation series of 84 FLs, in which 32% of t(14; 18)-negative FLs showed weak or absent CD10 expression and 91% an increased Ki67 proliferation rate. Although overall survival did not differ between FL with and without t(14; 18), our findings suggest distinct molecular features of t(14; 18)-negative FL. (Blood. 2009; 114: 826-834)