title: Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations.
abstract: 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, NFkappaB, 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.
authors.affiliation: Institute of Pathology, University of Wuerzburg, Josef-Schneider-Strasse 2, Wuerzburg, Germany.
authors.forename: Ellen
authors.initials: E
authors.lastname: Leich
authors.forename: Itziar
authors.initials: I
authors.lastname: Salaverria
authors.forename: Silvia
authors.initials: S
authors.lastname: Bea
authors.forename: Andreas
authors.initials: A
authors.lastname: Zettl
authors.forename: George
authors.initials: G
authors.lastname: Wright
authors.forename: Victor
authors.initials: V
authors.lastname: Moreno
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Wing-Chung
authors.initials: WC
authors.lastname: Chan
authors.forename: Rita M
authors.initials: RM
authors.lastname: Braziel
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimsza
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Andrew
authors.initials: A
authors.lastname: Lister
authors.forename: Jude
authors.initials: J
authors.lastname: Fitzgibbon
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: Elena M
authors.initials: EM
authors.lastname: Hartmann
authors.forename: Hans-Konrad
authors.initials: HK
authors.lastname: Mueller-Hermelink
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
mesh_terms: D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D005784:Gene Amplification / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2