Molecular profiling reveals prognostically significant subtypes of canine lymphoma

A. M. Frantz, A. L. Sarver, D. Ito, T. L. Phang, A. Karimpour-Fard, M. C. Scott, V. E O Valli, K. Lindblad-Toh, K. E. Burgess, B. D. Husbands, M. S. Henson, A. Borgatti, W. C. Kisseberth, L. E. Hunter, M. Breen, T. D. O'Brien, Jaime F. Modiano

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)693-703
Number of pages11
JournalVeterinary pathology
Volume50
Issue number4
DOIs
StatePublished - Aug 2013

Bibliographical note

Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by grants 2254 (JFM and MB), 615 (JFM, MB, and LEH), and 1113 (TDO and JFM) from the AKC Canine Health Foundation; grant D10-CA-501 (JFM, MB, KLT) from the Golden Retriever Foundation and Morris Animal Foundation; grants P30CA046934 (UCCC Core) and P30CA077598 (MCC Core) from the National Institutes of Health, by the Starlight Fund, the Land of PureGold Foundation, the WillPower Fund, and other philanthropic donations to the University of Minnesota Animal Cancer Care and Research Program and by the Companion Animal Health Foundation and a Tufts University internal seed grants (KEB). AMF was supported by the DVM/PhD combined degree program of the College of Veterinary Medicine, University of Minnesota, by a predoctoral fellowship from Morris Animal Foundation (D09CA-405) and by a doctoral dissertation fellowship from the Graduate School, University of Minnesota. DI is the recipient of a Morris Animal Foundation FIRST Award (D12CA-302). KLT is the recipient of a EURYI award from the ESF.

Keywords

  • Canine
  • Gene expression profiling
  • Lymphoma subclassification
  • Prognostication

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