title: Molecular profiling reveals prognostically significant subtypes of canine lymphoma.
abstract: We performed genomewide gene expression analysis of 35 samples representing 6 common histologic subtypes of canine lymphoma and bioinformatics analyses to define their molecular characteristics. Three major groups were defined on the basis of gene expression profiles: (1) low-grade T-cell lymphoma, composed entirely by T-zone lymphoma; (2) high-grade T-cell lymphoma, consisting of lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma not otherwise specified; and (3) B-cell lymphoma, consisting of marginal B-cell lymphoma, diffuse large B-cell lymphoma, and Burkitt lymphoma. Interspecies comparative analyses of gene expression profiles also showed that marginal B-cell lymphoma and diffuse large B-cell lymphoma in dogs and humans might represent a continuum of disease with similar drivers. The classification of these diverse tumors into 3 subgroups was prognostically significant, as the groups were directly correlated with event-free survival. Finally, we developed a benchtop diagnostic test based on expression of 4 genes that can robustly classify canine lymphomas into one of these 3 subgroups, enabling a direct clinical application for our results.
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, Minnesota, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Frantz
authors.forename: A L
authors.initials: AL
authors.lastname: Sarver
authors.forename: D
authors.initials: D
authors.lastname: Ito
authors.forename: T L
authors.initials: TL
authors.lastname: Phang
authors.forename: A
authors.initials: A
authors.lastname: Karimpour-Fard
authors.forename: M C
authors.initials: MC
authors.lastname: Scott
authors.forename: V E O
authors.initials: VE
authors.lastname: Valli
authors.forename: K
authors.initials: K
authors.lastname: Lindblad-Toh
authors.forename: K E
authors.initials: KE
authors.lastname: Burgess
authors.forename: B D
authors.initials: BD
authors.lastname: Husbands
authors.forename: M S
authors.initials: MS
authors.lastname: Henson
authors.forename: A
authors.initials: A
authors.lastname: Borgatti
authors.forename: W C
authors.initials: WC
authors.lastname: Kisseberth
authors.forename: L E
authors.initials: LE
authors.lastname: Hunter
authors.forename: M
authors.initials: M
authors.lastname: Breen
authors.forename: T D
authors.initials: TD
authors.lastname: O'Brien
authors.forename: J F
authors.initials: JF
authors.lastname: Modiano
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D019295:Computational Biology; D018572:Disease-Free Survival; D004283:Dog Diseases / Q000145:classification* / Q000401:mortality / Q000473:pathology; D004285:Dogs; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study / Q000662:veterinary; D016130:Immunophenotyping; D016393:Lymphoma, B-Cell / Q000145:classification / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D016399:Lymphoma, T-Cell / Q000145:classification / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm
keywords: canine; gene expression profiling; lymphoma subclassification; prognostication