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: 10.45). 11/2008; 113(3):635-45. DOI: 10.1182/blood-2008-02-140996
Source: PubMed


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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    • "Thus , in conjunction with detecting rearranged and somatically mutated IGHV genes , the gene expression analysis of our cases is indicative of memory B - cell derivation of non - splenic MZLs . Our results corroborate and extend the findings of Chng et al ( 2009 ) who reported similarities between the majority of pulmonary MZL expression profiles and marginal zone and memory B - cell profiles , whereas genes expressed in GC B - cells were under - represented . This is consistent with the critical role for antigen stimulation in disease pathogenesis , demonstrated for subtypes of MZL and the association of subsets with autoimmune disorders ( Swerdlow et al , 2008 ) . "
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    • "Family A/RZ RGS17/RGSZ2 " in prostate cancer [99]; " in lung cancer [99] RGS19/GAIP " in ovarian cancer [53]; regulates wnt/b-catenin signaling [100]; binding partner GIPC down-regulated in primary kidney tumors, colorectal tumors, gastric cancer, and prostate cancer [101] RGS20/RGSZ1 " in melanoma [102] Family B/R4 RGS1 " in melanoma [55]; " in head and neck squamous cell carcinoma [103]; " in adult T-cell leukemia [70]; " in renal cell carcinoma [54]; " in ovarian cancer [54]; " in cervical cancer [104]; " in mantle cell lymphoma [81] RGS2 # in ovarian cancer [53]; " in breast cancer [65]; " in fibrolamellar carcinoma [105]; # in prostate cancer [17]; # in acute myeloid leukemia [69]; " in mantle cell lymphoma [81] RGS3 " in docetaxel resistant breast cancers [106]; " associated with enhanced glioma cell motility [71]; " in soft tissue sarcomas [107] RGS4 " associated with enhanced glioma cell motility [71]; " in thyroid carcinoma [66]; # in ovarian cancer [53] RGS5 " in hepatocellular carcinoma [61]; " in breast cancer, melanoma, multiple myeloma, ovarian cancer, and acute myeloid leukemia [98]; " in fibrolamellar carcinoma [105] RGS8 N/A RGS13 # in mantle cell lymphoma [59]; " in B-and T-cell lymphoma [108] RGS16 " in pediatric high hyperdiploid acute lymphoblastic leukemias [109]; " in pineal parenchymal tumors [110]; p53 target gene in colorectal cancer [111] RGS18 N/A "
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