Small lymphocytic lymphoma, marginal zone B-cell lymphoma, and mantle cell lymphoma exhibit distinct gene-expression profiles allowing molecular diagnosis.
Non-germinal center small B-cell lymphomas represent a heterogeneous group of non-Hodgkin lymphomas, the most frequent histologic subtypes being small lymphocytic lymphoma (SLL), splenic marginal zone B-cell lymphoma (MZL), and mantle cell lymphoma (MCL). In order to identify genomic signatures specific for each disease, we analyzed 128 primary tumors using high-density microarrays. Several clusters of genes significantly discriminated the 3 histologic subtypes. Genes associated with cell adhesion, angiogenesis, and inhibition of apoptosis were up-regulated in SLL. Genes associated with intracellular signaling via the AKT1 pathway were up-regulated in splenic MZL. Genes associated with cell cycle control and multidrug resistance were up-regulated in MCL. Using 44 genes selected within the gene clusters discriminant for the 3 lymphoma subtypes, we generated a class prediction score that allowed us to classify the 3 entities in 96% of the cases, including borderline cases. Whereas specific transcriptional profiles easily distinguished all MZL samples, SLL samples, and most of the MCL samples into separate groups, few MCL cases exhibited MZL-type transcriptional profiles. This study demonstrates that SLL, splenic MZL, and MCL possess specific transcriptional profiles that may be relevant to the pathogenesis and the diagnosis of these histologic subtypes.
Thieblemont
Catherine
C
Service d'hématologie, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France. catherine.thieblemont@chu-lyon.fr
Nasser
Valéry
V
Felman
Pascale
P
Leroy
Karen
K
Gazzo
Sophie
S
Callet-Bauchu
Evelyne
E
Loriod
Béatrice
B
Granjeaud
Samuel
S
Gaulard
Philippe
P
Haioun
Corinne
C
Traverse-Glehen
Alexandra
A
Baseggio
Lucile
L
Bertucci
François
F
Birnbaum
Daniel
D
Magrangeas
Florence
F
Minvielle
Stéphane
S
Avet-Loiseau
Hervé
H
Salles
Gilles
G
Coiffier
Bertrand
B
Berger
Françoise
F
Houlgatte
Rémi
R
D001706:Biopsy; D003937:Diagnosis, Differential; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D020522:Lymphoma, Mantle-Cell / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D014066:Palatine Tonsil / Q000473:pathology; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D015203:Reproducibility of Results; D013154:Spleen / Q000473:pathology
D012334:RNA, Neoplasm