Molecular profiling reveals prognostically significant subtypes of canine lymphoma

Vet Pathol. 2013 Jul;50(4):693-703. doi: 10.1177/0300985812465325. Epub 2012 Nov 2.

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.

Keywords: canine; gene expression profiling; lymphoma subclassification; prognostication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism*
  • Cohort Studies
  • Computational Biology
  • Disease-Free Survival
  • Dog Diseases / classification*
  • Dog Diseases / mortality
  • Dog Diseases / pathology
  • Dogs
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genome-Wide Association Study / veterinary
  • Immunophenotyping
  • Lymphoma, B-Cell / classification
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell / veterinary*
  • Lymphoma, T-Cell / classification
  • Lymphoma, T-Cell / metabolism
  • Lymphoma, T-Cell / pathology
  • Lymphoma, T-Cell / veterinary*
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • RNA, Neoplasm / genetics

Substances

  • Biomarkers, Tumor
  • RNA, Neoplasm