Article

Gene expression profiling of pulmonary mucosa-associated lymphoid tissue lymphoma identifies new biologic insights with potential diagnostic and therapeutic applications.

Department of Hematology-Oncology, Comprehensive Cancer Center, Mayo Clinic, Scottsdale, AZ, USA.
Blood (impact factor: 9.9). 11/2008; 113(3):635-45. DOI:10.1182/blood-2008-02-140996 pp.635-45
Source: PubMed

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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Keywords

chemokine signaling pathways
 
comprehensive gene expression profiling
 
deregulated genes
 
deregulated pathways
 
different biologic characteristics
 
distinct molecular subsets
 
distinct pathologic features
 
genes
 
individual cases
 
MALT1 translocations
 
marginal zone/memory B-cell profile
 
normal lymphocytes
 
plasmacytic differentiation
 
primary pulmonary mucosa-associated lymphoid tissue
 
prominent plasma cell gene signature
 
prominent T-cell signature
 
RGS13 expression
 
T-cell lymphomas
 
therapeutic targets
 
trisomy 3