Gene Expression Profile of Nodal Marginal Zone Lymphoma. The Search for Diagnostic Markers
JA Arribas, Y Campos-Martin, M Sanchez-Beato, G Roncador, P Algara, G Kanellis, S Montes-Moreno, MA Piris, M Mollejo. Hospital Virgen de la Salud, SESCAM, Toledo, Spain; CNIO, Madrid, Spain
Background: Nodal marginal zone lymphoma (NMZL) is a small B-cell neoplasm whose molecular pathogenesis is still essentially unknown. The differential diagnosis with other small B cell lymphomas, as Follicular Lymphoma (FL) or other MZL arising in MALT or spleen is hampered by the lack of consistent diagnostic markers. The purpose of this study is to improve the knowledge of the molecular mechanism of this lymphoid neoplasia, selecting a set of possible NMZL markers to be explored in paraffin sections.
Design: Frozen tissue blocks from 17 NMZL and 8 reactive lymph nodes were analyzed. For comparison purposes, lymph nodes infiltrated by Follicular Lymphoma (16 cases), Splenic marginal zone lymphoma (4 cases) and MALT Marginal zone Lymphoma (5 cases) were included. Cases were diagnosed according to WHO classification criteria. ADN was amplified for studying the IgVH somatic mutation. High-quality total RNA was purified and amplified for microarray hybridization on Human Whole Oligo Microarray (4x44k, Agilent Technologies). Statistical analyses were performed by using GEPAS, Babelomics and GSEA.
Results: The NMZL signature contains genes related to BCR signaling, memory B-cell signature, apoptosis, inflammation, Rho GTPases, NFkB and TNF pathway, such as: CXXC5, ATP13A1, LYN, KCNN4, BTG2, CD82, CD81, SMARCB1, PTPN1, BBC3, REL A, SYK, UBC, TGFB1, COL9A3, GRB2, NFKBIB, TACI, PIK4CB, BLK, RAC2. Of the interest, the NMZL signature include genes associated to marginal zone, like TACI, RAC2, COL9A3. Additionally, comparision of the gene expression profiles of NMZL and FL subtypes revealed a set of genes differentially expresed in both groups, such as TACI or MNDA for NMZL and BCL6 and CD10 (MME) for FL.
Conclusions: Our study identified new candidate diagnostic molecules for NMZL, which could provide useful diagnostic and prognostic markers for improving the diagnosis accuracy in these tumors.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 132, Tuesday Morning