Submitted February 25, 2008
Accepted September 1, 2008
Gene expression profiling of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma identifies new biological insights with potential diagnostic and therapeutic applications
Wee J Chng, Ellen D Remstein, Rafael Fonseca, P Leif Bergsagel, Julie A Vrana, Paul J. Kurtin, and Ahmet Dogan*
Department of Hematology-Oncology, Comprehensive Cancer Center, Mayo Clinic, Scottsdale, AZ, United States
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States
* Corresponding author; email: dogan.ahmet{at}mayo.edu.
We conducted comprehensive gene expression profiling (GEP) of primary pulmonary mucosa-associated lymphoid tissue lymphoma (MALT) (n=33) and compared the results to GEP of other B and T cell lymphomas and normal lymphocytes in order 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 two 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 NFKB 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 a number of genes with very high ('spiked') expression in individual cases, we identified clusters with different biological 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.
