title: MicroRNA profiles of t(14;18)-negative follicular lymphoma support a late germinal center B-cell phenotype.
abstract: A total of 90% of follicular lymphomas (FLs) harbor the translocation t(14;18) leading to deregulated BCL2 expression. Conversely, 10% of FLs lack the t(14;18), and the majority of these FLs do not express BCL2. The molecular features of t(14;18)-negative FLs remain largely unknown. We performed microRNA expression analysis in 32 FL grades 1 to 3A, including 17 t(14;18)-positive FLs, 9 t(14;18)-negative FLs without BCL2 expression, and 6 t(14;18)-negative FLs with BCL2 expression. MicroRNA profiles were correlated with corresponding mRNA expression patterns, and potential targets were investigated by quantitative PCR and immunohistochemistry in an independent validation series of 83 FLs. Statistical analysis identified 17 microRNAs that were differentially expressed between t(14;18)-positive FLs and t(14;18)-negative FLs. The down-regulation of miR-16, miR-26a, miR-101, miR-29c, and miR138 in the t(14;18)-negative FL subset was associated with profound mRNA expression changes of potential target genes involving cell cycle control, apoptosis, and B-cell differentiation. miR-16 target CHEK1 showed increased expression in t(14;18)-negative FLs, whereas TCL1A expression was reduced, in line with a partial loss of the germinal center B-cell phenotype in this FL subset. In conclusion, t(14;18)-negative FL have distinct microRNA profiles that are associated with an increased proliferative capacity and a "late" germinal center B-cell phenotype.
authors.affiliation: Institute of Pathology, University of Würzburg, Josef-Schneider-Strasse 2, Würzburg, Germany.
authors.forename: Ellen
authors.initials: E
authors.lastname: Leich
authors.forename: Alberto
authors.initials: A
authors.lastname: Zamo
authors.forename: Heike
authors.initials: H
authors.lastname: Horn
authors.forename: Eugenia
authors.initials: E
authors.lastname: Haralambieva
authors.forename: Bernhard
authors.initials: B
authors.lastname: Puppe
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: Jude
authors.initials: J
authors.lastname: Fitzgibbon
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: Hans-Konrad
authors.initials: HK
authors.lastname: Mueller-Hermelink
authors.forename: Mariarita
authors.initials: M
authors.lastname: Calaminici
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Luis
authors.initials: L
authors.lastname: Hernández
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
mesh_terms: D000071877:Checkpoint Kinase 1; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D015331:Cohort Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018858:Germinal Center / Q000473:pathology; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology*; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D010641:Phenotype; D011494:Protein Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C090851:TCL1A protein, human; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1