Transformation of follicular lymphoma to diffuse large B-cell lymphoma proceeds by distinct oncogenic mechanisms.
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.
Davies
Andrew J
AJ
Cancer Research UK Medical Oncology Unit, St Bartholomew's Hospital, London, UK. andrew.davies@cancer.org.uk
Rosenwald
Andreas
A
Wright
George
G
Lee
Abigail
A
Last
Kim W
KW
Weisenburger
Dennis D
DD
Chan
Wing C
WC
Delabie
Jan
J
Braziel
Rita M
RM
Campo
Elias
E
Gascoyne
Randy D
RD
Jaffe
Elaine S
ES
Muller-Hermelink
Konrad
K
Ott
German
G
Calaminici
Maria
M
Norton
Andrew J
AJ
Goff
Lindsey K
LK
Fitzgibbon
Jude
J
Staudt
Louis M
LM
Andrew Lister
T
T
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
D016159:Tumor Suppressor Protein p53