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Transformation of follicular lymphoma to diffuse large B‐cell lymphoma proceeds by distinct oncogenic mechanisms
Author(s) -
Davies Andrew J.,
Rosenwald Andreas,
Wright George,
Lee Abigail,
Last Kim W.,
Weisenburger Dennis D.,
Chan Wing C.,
Delabie Jan,
Braziel Rita M.,
Campo Elias,
Gascoyne Randy D.,
Jaffe Elaine S.,
Konrad MullerHermelink H.,
Ott German,
Calaminici Maria,
Norton Andrew J.,
Goff Lindsey K.,
Fitzgibbon Jude,
Staudt Louis M.,
Andrew Lister T.
Publication year - 2007
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2006.06439.x
Subject(s) - follicular lymphoma , biology , germinal center , lymphoma , cancer research , malignant transformation , cell growth , gene expression profiling , immunohistochemistry , b cell , gene , pathology , gene expression , immunology , genetics , medicine , antibody
Summary 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.