title: Gene profiling of canine B-cell lymphoma reveals germinal center and postgerminal center subtypes with different survival times, modeling human DLBCL.
abstract: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype, and fewer than half of patients are cured with standard first-line therapy. To improve therapeutic options, better animal models that accurately mimic human DLBCL (hDLBCL) are needed. Canine DLBCL, one of the most common cancers in veterinary oncology, is morphologically similar to hDLBCL and is treated using similar chemotherapeutic protocols. With genomic technologies, it is now possible to molecularly evaluate dogs as a potential large-animal model for hDLBCL. We evaluated canine B-cell lymphomas (cBCL) using immunohistochemistry (IHC) and gene expression profiling. cBCL expression profiles were similar in many ways to hDLBCLs. For instance, a subset had increased expression of NF-κB pathway genes, mirroring human activated B-cell (ABC)-type DLBCL. Furthermore, immunoglobulin heavy chain ongoing mutation status, which is correlated with ABC/germinal center B-cell cell of origin in hDLBCL, separated cBCL into two groups with statistically different progression-free and overall survival times. In contrast with hDLBCL, cBCL rarely expressed BCL6 and MUM1/IRF4 by IHC. Collectively, these studies identify molecular similarities to hDLBCL that introduce pet dogs as a representative model of hDLBCL for future studies, including therapeutic clinical trials.
authors.affiliation: Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA. kristy_richards@med.unc.edu
authors.forename: Kristy L
authors.initials: KL
authors.lastname: Richards
authors.forename: Alison A
authors.initials: AA
authors.lastname: Motsinger-Reif
authors.forename: Hsiao-Wei
authors.initials: HW
authors.lastname: Chen
authors.forename: Yuri
authors.initials: Y
authors.lastname: Fedoriw
authors.forename: Cheng
authors.initials: C
authors.lastname: Fan
authors.forename: Dahlia M
authors.initials: DM
authors.lastname: Nielsen
authors.forename: George W
authors.initials: GW
authors.lastname: Small
authors.forename: Rachael
authors.initials: R
authors.lastname: Thomas
authors.forename: Chris
authors.initials: C
authors.lastname: Smith
authors.forename: Sandeep S
authors.initials: SS
authors.lastname: Dave
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.forename: Matthew
authors.initials: M
authors.lastname: Breen
authors.forename: Luke B
authors.initials: LB
authors.lastname: Borst
authors.forename: Steven E
authors.initials: SE
authors.lastname: Suter
mesh_terms: D000293:Adolescent; D000818:Animals; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D018858:Germinal Center / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D059467:Transcriptome; D000099218:Interferon Regulatory Factor-4
chemical_list: D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D050835:Interferon Regulatory Factors; D016328:NF-kappa B; D051560:Proto-Oncogene Proteins c-bcl-6; D000099218:Interferon Regulatory Factor-4; C084103:BCL6 protein, human