Gene expression profiling of pulmonary mucosa-associated lymphoid tissue lymphoma identifies new biologic insights with potential diagnostic and therapeutic applications.
ABSTRACT We conducted comprehensive gene expression profiling (GEP) of primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma (n = 33) and compared the results to GEP of other B- and T-cell lymphomas and normal lymphocytes to identify novel markers and deregulated pathways. MALT has a prominent T-cell signature and a marginal zone/memory B-cell profile. Four novel transcripts were specifically overexpressed in MALT, and 2 of these, MMP7 and SIGLEC6, were validated at the protein level. GEP also revealed distinct molecular subsets in MALT. One subset, characterized by MALT1 translocations, showed overexpression of nuclear factor-kappaB (NF-KB) pathway genes but also was enriched for chemokine signaling pathways. Another subset showed increased plasma cells and a prominent plasma cell gene signature. By analyzing several genes with very high ("spiked") expression in individual cases, we identified clusters with different biologic characteristics, such as samples with MALT1 translocations having high expression of MALT1 and RARA, samples with plasmacytic differentiation having high FKBP11 expression, and samples with high RGS13 expression tending to have trisomy 3 and reactive follicles. In conclusion, MALT subgroups with distinct pathologic features defined by distinct groups of deregulated genes were identified. These genes could represent novel diagnostic and therapeutic targets.
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ABSTRACT: Three distinct categories of marginal zone lymphomas (MZLs) are currently recognized, principally based on their site of occurrence. They are thought to represent unique entities, but the relationship of one subtype with another is poorly understood. We investigated 17 non-splenic MZLs (seven nodal, 10 extranodal) by gene expression profiling to distinguish between subtypes and determine their cell of origin. Our findings suggest biological inter-relatedness of these entities despite occurrence at different locations and associations with possibly different aetiologies. Furthermore, the expression profiles of non-splenic MZL were similar to memory B cells.British Journal of Haematology 08/2011; 155(3):362-5. DOI:10.1111/j.1365-2141.2011.08841.x · 4.96 Impact Factor
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ABSTRACT: The regulator of G-protein signaling (RGS) family is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). In recent years, GPCRs have been linked to the initiation and progression of multiple cancers; thus, regulators of GPCR signaling are also likely to be important to the pathophysiology of cancer. This review highlights recent studies detailing changes in RGS transcript expression during oncogenesis, single nucleotide polymorphisms in RGS proteins linked to lung and bladder cancers, and specific roles for RGS proteins in multiple cancer types.Biochemical pharmacology 07/2009; 78(10):1289-97. DOI:10.1016/j.bcp.2009.06.028 · 4.65 Impact Factor
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ABSTRACT: Elegant animal models of lymphocyte traffic have uncovered routes of lymphocyte movement between and within tissues. Routes of human lymphocyte migration cannot always be extrapolated from animal studies and investigating this in vivo is particularly challenging. In this commentary, we consider the migratory properties of low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) and describe a migratory route between the human mucosa and splenic marginal zone.Mucosal Immunology 08/2009; 2(5):380-2. DOI:10.1038/mi.2009.91 · 7.54 Impact Factor