Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes.
Burkitt lymphoma (BL) is classified into 3 clinical subsets: endemic, sporadic, and immunodeficiency-associated BL. So far, possible differences in their gene expression profiles (GEPs) have not been investigated. We studied GEPs of BL subtypes, other B-cell lymphomas, and B lymphocytes; first, we found that BL is a unique molecular entity, distinct from other B-cell malignancies. Indeed, by unsupervised analysis all BLs clearly clustered apart of other lymphomas. Second, we found that BL subtypes presented slight differences in GEPs. Particularly, they differed for genes involved in cell cycle control, B-cell receptor signaling, and tumor necrosis factor/nuclear factor κB pathways. Notably, by reverse engineering, we found that endemic and sporadic BLs diverged for genes dependent on RBL2 activity. Furthermore, we found that all BLs were intimately related to germinal center cells, differing from them for molecules involved in cell proliferation, immune response, and signal transduction. Finally, to validate GEP, we applied immunohistochemistry to a large panel of cases and showed that RBL2 can cooperate with MYC in inducing a neoplastic phenotype in vitro and in vivo. In conclusion, our study provided substantial insights on the pathobiology of BLs, by offering novel evidences that may be relevant for its classification and possibly future treatment.
Department of Hematology and Oncological Sciences L. and A. Seràgnoli, Hematopathology Unit, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, Bologna, Italy. pierpaolo.piccaluga@unibo.it
Pier Paolo
PP
Piccaluga
Giulia
G
De Falco
Manjunath
M
Kustagi
Anna
A
Gazzola
Claudio
C
Agostinelli
Claudio
C
Tripodo
Eleonora
E
Leucci
Anna
A
Onnis
Annalisa
A
Astolfi
Maria Rosaria
MR
Sapienza
Cristiana
C
Bellan
Stefano
S
Lazzi
Lynnette
L
Tumwine
Michael
M
Mawanda
Martin
M
Ogwang
Valeria
V
Calbi
Serena
S
Formica
Andrea
A
Califano
Stefano A
SA
Pileri
Lorenzo
L
Leoncini
D000818:Animals; D002051:Burkitt Lymphoma / Q000145:classification* / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D046228:Microarray Analysis; D009368:Neoplasm Transplantation; D010641:Phenotype; D014183:Transplantation, Heterologous