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 Blood, 15 January 2009, Vol. 113, No. 3, pp. 635-645.
Prepublished online as a Blood First Edition Paper on October 30, 2008; DOI 10.1182/blood-2008-02-140996.

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LYMPHOID NEOPLASIA

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

Wee J. Chng1,*, Ellen D. Remstein2,*, Rafael Fonseca1, P. Leif Bergsagel1, Julie A. Vrana2, Paul J. Kurtin2, and Ahmet Dogan2

1 Department of Hematology-Oncology, Comprehensive Cancer Center, Mayo Clinic, Scottsdale, AZ; and 2 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN

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-{kappa}B (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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