title: Transformation of follicular lymphoma to diffuse large B-cell lymphoma proceeds by distinct oncogenic mechanisms.
abstract: This study was undertaken to further elucidate the biological mechanisms underlying the frequent event of transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL). The gene expression profiles of 20 paired lymph node biopsies, derived from the same patient pre- and post-transformation, were analysed using the Lymphochip cDNA microarray. TP53 mutation analysis was performed and copy number alterations at the c-REL and CDNK2A examined. Immunohistochemistry was performed on an independent panel of paired transformation paraffin-embedded samples. Transformed follicular lymphoma was predominantly of the germinal centre B-like phenotype both at the mRNA and protein level. Despite this homogeneity, transformation proceeded by at least two pathways. One mechanism was characterised by high proliferation, as assessed by the co-ordinately expressed genes of the proliferation signature. This group was associated with the presence of recurrent oncogenic abnormalities. In the remaining cases, proliferation was not increased and transformation proceeded by alternative routes as yet undetermined. Genes involved in cellular proliferation prevailed amongst those that were significantly increased upon transformation and T cell and follicular dendritic-associated genes predominated amongst those that decreased. t-FL is a germinal centre B (GCB)-like malignancy that evolves by two pathways, one that is similar in proliferation rate to the antecedent FL and the other that has a higher proliferation rate and is characterised by the presence of recognised oncogenic abnormalities.
authors.affiliation: Cancer Research UK Medical Oncology Unit, St Bartholomew's Hospital, London, UK. andrew.davies@cancer.org.uk
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Davies
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: George
authors.initials: G
authors.lastname: Wright
authors.forename: Abigail
authors.initials: A
authors.lastname: Lee
authors.forename: Kim W
authors.initials: KW
authors.lastname: Last
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.forename: Rita M
authors.initials: RM
authors.lastname: Braziel
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Konrad
authors.initials: K
authors.lastname: Muller-Hermelink
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Maria
authors.initials: M
authors.lastname: Calaminici
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Norton
authors.forename: Lindsey K
authors.initials: LK
authors.lastname: Goff
authors.forename: Jude
authors.initials: J
authors.lastname: Fitzgibbon
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: T
authors.initials: T
authors.lastname: Andrew Lister
mesh_terms: D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D020869:Gene Expression Profiling; D016259:Genes, myc; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D016159:Tumor Suppressor Protein p53