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GEO help: Mouse over screen elements for information. |
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Status |
Public on Nov 01, 2007 |
Title |
Gene expression analysis of B-NHL from λMYC, λMYC/IµHABCL6, λMYC/AIDKO and λMYC/IµHABCL6/AIDKO mouse models |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Most human B cell lymphomas (B-NHL) are derived from germinal centers (GCs), the structure where B-cells undergo class switch recombination (CSR) and somatic hypermutation (SHM) and are selected for high-affinity antibody production. The pathogenesis of B-NHL is associated with distinct genetic lesions, including chromosomal translocations and aberrant somatic hypermutation, which appear to arise from mistakes occurring during CSR and SHM. To ascertain the role of CSR and SHM in lymphomagenesis, we crossed three oncogene-driven (MYC, BCL6, MYC/BCL6) mouse models of B cell lymphoma with mice lacking activation-induced cytidine deaminase (AID), the enzyme required for both processes. We show that AID deficiency prevents BCL6-dependent, GC-derived B-NHL, while it has no impact on the formation of MYC-driven, pre-GC lymphomas. Accordingly, abrogation of AID is associated with the disappearance of both CSR- and SHM-mediated structural alterations, including cMYC-IgH chromosomal translocations and aberrant SHM. These results demonstrate that AID is required for GC-derived lymphomagenesis, providing direct support to the notion that errors in AID-mediated antigen-receptor gene modification events represent major contributors to the pathogenesis of human B-NHL. Keywords: Phenotypic characterization of tumors developing in oncogene-driven mouse models of lymphomas
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Overall design |
Nodal B-NHL from 5 MYC, 7 MYC/AIDKO, 12 MYC/HABCL6 and 6 MYC/HABCL6/AIDKO mice were analyzed in this study. Total RNA was extracted from frozen tumor biopsies and processed according to Affymetrix standard protocols
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Contributor(s) |
Pasqualucci L, Dalla-Favera R |
Citation(s) |
18066064 |
Submission date |
Oct 05, 2007 |
Last update date |
Jan 10, 2023 |
Contact name |
Laura Pasqualucci |
E-mail(s) |
lp171@cumc.columbia.edu
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Organization name |
Columbia University
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Department |
Institute for Cancer Genetics
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Street address |
1130 St Nicholas Avenue
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City |
New York |
State/province |
NY |
ZIP/Postal code |
10032 |
Country |
USA |
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Platforms (1) |
GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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Samples (28)
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Relations |
BioProject |
PRJNA102863 |
Supplementary file |
Size |
Download |
File type/resource |
GSE9249_RAW.tar |
96.5 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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