title: MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma.
abstract: Diffuse large B cell lymphoma (DLBCL) is an aggressive malignancy that accounts for nearly 40% of all lymphoid tumors. This heterogeneous disease can be divided into germinal center B cell-like (GCB) and activated B cell-like (ABC) subtypes by gene expression and immunohistochemical profiling. Using microarray analysis on prototypic cell lines, we identified microRNAs (miR-155, miR-21 and miR-221) that were more highly expressed in ABC-type than GCB-type cell lines. These microRNAs were over-expressed in de novo DLBCL (n = 35), transformed DLBCL (n = 14) and follicular center lymphoma cases (n = 27) compared to normal B cells. Consistent with the cell line model, expression levels were higher in DLBCL cases with an ABC-type immunophenotype than those that were GCB-type (p < 0.05). Moreover, using multivariate analysis we found that expression of miR-21 was an independent prognostic indicator in de novo DLBCL (p < 0.05). Interestingly, expression levels of both miR-155 and miR-21 were also higher in nonmalignant ABC than in GCB cells. As we also demonstrate that expression of microRNAs can be measured reliably from routine paraffin-embedded biopsies of more than 8-years-old (p < 0.001), we suggest that microRNAs could be clinically useful molecular markers for DLBCL as well as other cancers.
authors.affiliation: Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom. charles.lawrie@ndcls.ox.ac.uk
authors.forename: Charles H
authors.initials: CH
authors.lastname: Lawrie
authors.forename: Shamit
authors.initials: S
authors.lastname: Soneji
authors.forename: Teresa
authors.initials: T
authors.lastname: Marafioti
authors.forename: Christopher D O
authors.initials: CD
authors.lastname: Cooper
authors.forename: Stefano
authors.initials: S
authors.lastname: Palazzo
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Paterson
authors.forename: Helen
authors.initials: H
authors.lastname: Cattan
authors.forename: Tariq
authors.initials: T
authors.lastname: Enver
authors.forename: Rachel
authors.initials: R
authors.lastname: Mager
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Boultwood
authors.forename: James S
authors.initials: JS
authors.lastname: Wainscoat
authors.forename: Christian S R
authors.initials: CS
authors.lastname: Hatton
mesh_terms: D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D011379:Prognosis; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs