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.
- SourceAvailable from: onlinelibrary.wiley.com[Show abstract] [Hide abstract]
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. · 4.94 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: This chapter summarizes the significance and molecular diagnostic detection of genetic abnormalities commonly associated with hematolymphoid neoplasms. Methodologic aspects of laboratory diagnosis are presented, as well as discussion of multiparameter genotyping of tumors for prognosis and the role of minimal residual disease monitoring in specific neoplasms.Hematology/oncology clinics of North America 09/2009; 23(4):903-33. · 2.05 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: This chapter provides an overview of lymphomas and related tumors presenting at extranodal locations. Commonalities and differences in the approach to diagnosis, staging, and their pathogenesis are summarized. Intrinsic tumors of the thymus are also discussed. KeywordsExtranodal lymphoma, incidence by site–Skin, lymphomas–Brain, lymphoma–Central nervous system, lymphoma–Head and neck, lymphoma–Thyroid, lymphoma–Lung, lymphoma–Small bowel, lymphoma–Liver–Lymphoma–Testes, adrenal, lymphoma–Ovary, lymphoma–Endometrium, lymphoma–Thymus, maturation–Thymus, B cells–Thymoma, classification–Thymic carcinoma–Lymphoblastic lymphoma, mediastinal–Hodgkin lymphoma, thymus–Mediastinal B-cell lymphoma, thymic origin12/2009: pages 477-501;