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
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.
Available from: Anke Reitter
- "Moreover, it is intriguingly to address whether the deregulated GdA/Siglec-6/(ERK)/c-Jun network could be responsible for the shallow invasion characteristic in preeclampsia placenta . Importantly, the gene and protein level of Siglec6 is specifically increased in primary pulmonary mucosa-associated lymphoid tissue (MALT) . Whether it has a role in the pathogenesis of the MALT remains to be clarified. "
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ABSTRACT: Tumor progression and pregnancy share many common features, such as immune tolerance and invasion. The invasion of trophoblasts in the placenta into the uterine wall is essential for fetal development, and is thus precisely regulated. Its deregulation has been implicated in preeclampsia, a leading cause for maternal and perinatal mortality and morbidity. Pathogenesis of preeclampsia remains to be defined. Microarray-based gene profiling has been widely used for identifying genes responsible for preeclampsia. In this review, we have summarized the recent data from the microarray studies with preeclamptic placentas. Despite the complex of gene signatures, suggestive of the heterogeneity of preeclampsia, these studies identified a number of differentially expressed genes associated with preeclampsia. Interestingly, most of them have been reported to be tightly involved in tumor progression. We have discussed these interesting genes and analyzed their potential molecular functions in preeclampsia, compared with their roles in malignancy development. Further investigations are warranted to explore the involvement in molecular network of each identified gene, which may provide not only novel strategies for prevention and therapy for preeclampsia but also a better understanding of cancer cells. The trophoblastic cells, with their capacity for proliferation and differentiation, apoptosis and survival, migration, angiogenesis and immune modulation by exploiting similar molecular pathways, make them a compelling model for cancer research.
Available from: Laura Pasqualucci
- "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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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.
Available from: Jillian Hurst
- "Family A/RZ RGS17/RGSZ2 " in prostate cancer ; " in lung cancer  RGS19/GAIP " in ovarian cancer ; regulates wnt/b-catenin signaling ; binding partner GIPC down-regulated in primary kidney tumors, colorectal tumors, gastric cancer, and prostate cancer  RGS20/RGSZ1 " in melanoma  Family B/R4 RGS1 " in melanoma ; " in head and neck squamous cell carcinoma ; " in adult T-cell leukemia ; " in renal cell carcinoma ; " in ovarian cancer ; " in cervical cancer ; " in mantle cell lymphoma  RGS2 # in ovarian cancer ; " in breast cancer ; " in fibrolamellar carcinoma ; # in prostate cancer ; # in acute myeloid leukemia ; " in mantle cell lymphoma  RGS3 " in docetaxel resistant breast cancers ; " associated with enhanced glioma cell motility ; " in soft tissue sarcomas  RGS4 " associated with enhanced glioma cell motility ; " in thyroid carcinoma ; # in ovarian cancer  RGS5 " in hepatocellular carcinoma ; " in breast cancer, melanoma, multiple myeloma, ovarian cancer, and acute myeloid leukemia ; " in fibrolamellar carcinoma  RGS8 N/A RGS13 # in mantle cell lymphoma ; " in B-and T-cell lymphoma  RGS16 " in pediatric high hyperdiploid acute lymphoblastic leukemias ; " in pineal parenchymal tumors ; p53 target gene in colorectal cancer  RGS18 N/A "
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ABSTRACT: The regulator of G-protein signaling (RGS) family is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). In recent years, GPCRs have been linked to the initiation and progression of multiple cancers; thus, regulators of GPCR signaling are also likely to be important to the pathophysiology of cancer. This review highlights recent studies detailing changes in RGS transcript expression during oncogenesis, single nucleotide polymorphisms in RGS proteins linked to lung and bladder cancers, and specific roles for RGS proteins in multiple cancer types.
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