MicroRNA expression, chromosomal alterations, and immunoglobulin variable heavy chain hypermutations in Mantle cell lymphomas.
The contribution of microRNAs (miR) to the pathogenesis of mantle cell lymphoma (MCL) is not well known. We investigated the expression of 86 mature miRs mapped to frequently altered genomic regions in MCL in CD5(+)/CD5(-) normal B cells, reactive lymph nodes, and purified tumor cells of 17 leukemic MCL, 12 nodal MCL, and 8 MCL cell lines. Genomic alterations of the tumors were studied by single nucleotide polymorphism arrays and comparative genomic hybridization. Leukemic and nodal tumors showed a high number of differentially expressed miRs compared with purified normal B cells, but only some of them were commonly deregulated in both tumor types. An unsupervised analysis of miR expression profile in purified leukemic MCL cells revealed two clusters of tumors characterized by different mutational status of the immunoglobulin genes, proliferation signature, and number of genomic alterations. The expression of most miRs was not related to copy number changes in their respective chromosomal loci. Only the levels of miRs included in the miR-17-92 cluster were significantly related to genetic alterations at 13q31. Moreover, overexpression of miR-17-5p/miR-20a from this cluster was associated with high MYC mRNA levels in tumors with a more aggressive behavior. In conclusion, the miR expression pattern of MCL is deregulated in comparison with normal lymphoid cells and distinguishes two subgroups of tumors with different biological features.
Navarro
Alba
A
Department of Pathology (Hematopathology Unit), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona.
Beà
Sílvia
S
Fernández
Verónica
V
Prieto
Miriam
M
Salaverria
Itziar
I
Jares
Pedro
P
Hartmann
Elena
E
Mozos
Anna
A
López-Guillermo
Armando
A
Villamor
Neus
N
Colomer
Dolors
D
Puig
Xavier
X
Ott
German
G
Solé
Francesc
F
Serrano
Sergi
S
Rosenwald
Andreas
A
Campo
Elías
E
Hernández
Luis
L
D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000276:immunology; D035683:MicroRNAs / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics*; D027041:Somatic Hypermutation, Immunoglobulin
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D035683:MicroRNAs; D012334:RNA, Neoplasm