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Series GSE9249 Query DataSets for GSE9249
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
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
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
Contributor(s) Pasqualucci L, Dalla-Favera R
Citation(s) 18066064
Submission date Oct 05, 2007
Last update date Feb 11, 2019
Contact name Laura Pasqualucci
Organization name Columbia University
Department Institute for Cancer Genetics
Street address 1130 St Nicholas Ave
City New York
State/province NY
ZIP/Postal code 10032
Country USA
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (28)
GSM234812 Lymphoma lambda MYCtg 1
GSM234813 Lymphoma lambda MYCtg 2
GSM234814 Lymphoma lambda MYCtg 3
BioProject PRJNA102863

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Supplementary file Size Download File type/resource
GSE9249_RAW.tar 96.5 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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