STANDARD_NAME SHIN_B_CELL_LYMPHOMA_CLUSTER_8 SYSTEMATIC_NAME M1392 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/SHIN_B_CELL_LYMPHOMA_CLUSTER_8 NAMESPACE MOUSE_GENE_SYMBOL DESCRIPTION_BRIEF Cluster 8 of genes distinguishing among different B lymphocyte neoplasms. DESCRIPTION_FULL Aside from Myc-activating translocations characteristic of plasmacytomas (PCT), little is known about genetic factors and signaling pathways responsible for the development of spontaneous B-cell lineage lymphomas of mice. Here, we characterized the transcriptional profiles of PCT, centroblastic diffuse large B-cell lymphomas (CBL), and high-grade splenic marginal zone B-cell lymphoma (MZL++) using high-throughput quantitative reverse transcription-PCR. Expression profiles of CBL and MZL++ were strikingly similar and quite unlike that of PCT. Among the genes expressed at significantly higher levels by PCT were a number involved in NOTCH signaling, a finding supported by gene set enrichment analyses of microarray data. To investigate the importance of this pathway, NOTCH signaling was blocked in PCT cell lines by treatment with a gamma-secretase inhibitor (GSI) or transduction of a dominant-negative mutant of MAML1. These treatments resulted in reduced expression of NOTCH transcriptional targets in association with impaired proliferation and increased apoptosis. GSI treatment of transformed plasma cells in a primary PCT also induced apoptosis. These results integrate NOTCH activation with oncogenic signaling pathways downstream of translocated Myc in the pathogenesis of mouse PCT, two signaling pathways also implicated in development of human multiple myeloma and T-cell lymphoblastic lymphoma. PMID 19010892 GEOID AUTHORS Shin DM,Shaffer DJ,Wang H,Roopenian DC,Morse HC 3rd CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 2S: Cluster = 8 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS Ccnb1,Ccnb2,Cd38,Cd80,Cdk2,Chek1,Fancg,Fas,Fasl,Gnas,H2afx,Hdac1,Icam1,Il15,Il1r2,Il21r,Il2ra,Itgam,Lmo1,Lyn,Mafb,Mafk,Mapk3,Mfng,Nbn,Nfkbia,Nfkbib,Psen1,Sfpi1,Smad7,Snai1,Sox4,Spn,Stat1,Tnfrsf13c,Tyrobp,Wnt3a GENE_SYMBOLS CCNB1,CCNB2,CD38,CD80,CDK2,CHEK1,FANCG,FAS,FASLG,GNAS,H2AX,HDAC1,ICAM1,IL15,IL1R2,IL21R,IL2RA,ITGAM,LMO1,LYN,MAFB,MAFK,MAPK3,MFNG,NBN,NFKBIA,NFKBIB,PSEN1,SPI1,SMAD7,SNAI1,SOX4,SPN,STAT1,TNFRSF13C,TYROBP,WNT3A FOUNDER_NAMES