Differences Between Follicular Lymphoma With and Without Translocation t(14;18)

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 regarding their immunohistochemical, genetic, molecular and clinical features. Within a previously published series of 184 FL grade 1-3A with available gene expression data, we identified 17 FL lacking the t(14;18). Comparative genomic hybridization and high resolution SNP array profiling demonstrated 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 revealed an enrichment of germinal center B-cell associated signatures in t(14;18)-positive FL, whereas activated B-cell like, NFB, 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 FL, in which 32% of t(14;18)-negative FL 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.

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Leich E, Salaverria I, Bea S, Zettl A, Wright G, Moreno V, Gascoyne RD, Chan WC, Braziel RM, Rimsza LM, Weisenburger DD, Delabie J, Jaffe ES, Lister A, Fitzgibbon J, Staudt LM, Hartmann EM, Mueller-Hermelink HK, Campo E, Ott G, Rosenwald A