Splenic Marginal Zone Lymphoma: Comprehensive Analysis of Gene Expression and miRNA Profiling
Manuela Mollejo, Alberto Arribas, Cristina Gomez-Abad, Margarita Sanchez-Beato, Nerea Martinez, Lorena Dilisio, Felipe Casado, Miguel A Cruz, Patrocinio Algara, Miguel A Piris. Hospital Virgen de la Salud, Toledo, Spain; NIMGenetics, Madrid, Spain; Fundación Investigación Biomédica, Hospital Universitario, Puerta de Hierro-Majadahonda, Madrid, Spain; Hospital Universitario Marqués de Valdecilla, Santander, Spain
Background: SMZL is an uncommon form of small B cell neoplasm infiltrating in the spleen, bone marrow and peripheral blood. The miRNA profile of SMZL has been investigated by several groups. who have obtained interesting results related with 7q loss, HCV presence or with normal spleen. Nevertheless, the miRNA changes in SMZL are yet to be comprehensively described. We aimed to carry out an integrated genomics study to improve our understanding of the molecular mechanisms involved in the pathogenesis of SMZL, and to suggest new targets, genes and miRNAs, with diagnostic and therapeutic potential.
Design: We have analyzed the gene expression and miRNA profiles of 31 SMZL cases. For comparison, seven spleens with reactive lymphoid hyperplasia, 10 spleens infiltrated by chronic lymphocytic leukemia, 12 spleens with follicular lymphoma, six spleens infiltrated by mantle cell lymphoma and 15 lymph nodes infiltrated by nodal marginal zone lymphoma were included. The results were validated by qRT-PCR in an independent series including 77 paraffin-embedded SMZLs.
Results: The SMZL miRNA signature had deregulated expression of 51 miRNAs. The most highly overexpressed miRNAs were miR-155, miR-21, miR-34a, miR-193b and miR-100, while the most repressed miRNAs were miR-377, miR-27b, miR-145, miR-376a and miR-424. MiRNAs located in 14q32-31 were underexpressed in SMZL compared with reactive lymphoid tisues and other B cell lymphomas. Finally, the GEP data were integrated with the miRNA profile to identify functional relationships between genes and deregulated miRNAs.
Conclusions: Our study reveals miRNAs that are deregulated in SMZL and identifies new candidate diagnostic molecules for SMZL.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 259, Tuesday Afternoon