Gene Set: PASQUALUCCI_LYMPHOMA_BY_GC_STAGE_UP

Standard name PASQUALUCCI_LYMPHOMA_BY_GC_STAGE_UP
Systematic name M6510
Brief description Genes up-regulated in post-GC, BCL6 [GeneID=604] dependent B cell non-Hodgkin's lymphoma (B-NHL) vs MYC [GeneID=4609] driven pre-GC lymphoma.
Full description or abstract Most human B cell non-Hodgkin's lymphomas (B-NHLs) derive from germinal centers (GCs), the structure in which B cells undergo somatic hypermutation (SHM) and class switch recombination (CSR) before being selected for high-affinity antibody production. The pathogenesis of B-NHL is associated with distinct genetic lesions, including chromosomal translocations and aberrant SHM, which arise from mistakes occurring during CSR and SHM. A direct link between these DNA remodeling events and GC lymphoma development, however, has not been demonstrated. Here we have crossed three mouse models of B cell lymphoma driven by oncogenes (Myc, Bcl6 and Myc/Bcl6; refs. 5,6) with mice lacking activation-induced cytidine deaminase (AID), the enzyme required for both CSR and SHM. We show that AID deficiency prevents Bcl6-dependent, GC-derived B-NHL, but has no impact on Myc-driven, pre-GC lymphomas. Accordingly, abrogation of AID is associated with the disappearance of CSR- and SHM-mediated structural alterations. These results show that AID is required for GC-derived lymphomagenesis, supporting the notion that errors in AID-mediated antigen-receptor gene modification processes are principal contributors to the pathogenesis of human B-NHL.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18066064   Authors: Pasqualucci L,Bhagat G,Jankovic M,Compagno M,Smith P,Muramatsu M,Honjo T,Morse HC 3rd,Nussenzweig MC,Dalla-Favera R
Exact source Table 2S: Z score > 0
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(show 97 gene sets from the same authors)
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Organism Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
Source platform AFFY_Mouse430
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Version history 3.0: First introduced

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