Chromosome Research

, Volume 23, Issue 4, pp 681–708 | Cite as

Genome-wide assessment of recurrent genomic imbalances in canine leukemia identifies evolutionarily conserved regions for subtype differentiation

  • Sarah C. Roode
  • Daniel Rotroff
  • Anne C. Avery
  • Steven E. Suter
  • Dorothee Bienzle
  • Joshua D. Schiffman
  • Alison Motsinger-Reif
  • Matthew Breen


Leukemia in dogs is a heterogeneous disease with survival ranging from days to years, depending on the subtype. Strides have been made in both human and canine leukemia to improve classification and understanding of pathogenesis through immunophenotyping, yet classification and choosing appropriate therapy remains challenging. In this study, we assessed 123 cases of canine leukemia (28 ALLs, 24 AMLs, 25 B-CLLs, and 46 T-CLLs) using high-resolution oligonucleotide array comparative genomic hybridization (oaCGH) to detect DNA copy number alterations (CNAs). For the first time, such data were used to identify recurrent CNAs and inclusive genes that may be potential drivers of subtype-specific pathogenesis. We performed predictive modeling to identify CNAs that could reliably differentiate acute subtypes (ALL vs. AML) and chronic subtypes (B-CLL vs. T-CLL) and used this model to differentiate cases with up to 83.3 and 95.8 % precision, respectively, based on CNAs at only one to three genomic regions. In addition, CGH datasets for canine and human leukemia were compared to reveal evolutionarily conserved copy number changes between species, including the shared gain of HSA 21q in ALL and ∼25 Mb of shared gain of HSA 12 and loss of HSA 13q14 in CLL. These findings support the use of canine leukemia as a relevant in vivo model for human leukemia and justify the need to further explore the conserved genomic regions of interest for their clinical impact.


Leukemia Canine Chromosome Comparative genomic hybridization Comparative genomics 



Acute lymphoblastic leukemia


Acute myeloid leukemia


Bacterial artificial chromosome


Canis familiaris


Chronic lymphocytic leukemia


Chronic myeloid leukemia


Chronic myelomonocytic leukemia


Chronic monocytic leukemia


Copy number aberration


Copy number variant


Fluorescence in situ hybridization


Genomic Identification of Significant Targets in Cancer


Homo sapiens




Oligonucleotide array comparative genomic hybridization


Single nucleotide polymorphism


T zone lymphoma


White blood cell

Supplementary material

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ESM 1(XLS 31 kb)
10577_2015_9475_MOESM2_ESM.xls (116 kb)
ESM 2(XLS 115 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Sarah C. Roode
    • 1
  • Daniel Rotroff
    • 2
  • Anne C. Avery
    • 3
  • Steven E. Suter
    • 4
    • 5
    • 6
  • Dorothee Bienzle
    • 7
  • Joshua D. Schiffman
    • 8
    • 9
  • Alison Motsinger-Reif
    • 2
    • 5
  • Matthew Breen
    • 1
    • 5
    • 6
  1. 1.Department of Molecular Biomedical Sciences, College of Veterinary MedicineNorth Carolina State UniversityRaleighUSA
  2. 2.Bioinformatics Research Center, Department of StatisticsNorth Carolina State UniversityRaleighUSA
  3. 3.Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical ScienceColorado State UniversityFort CollinsUSA
  4. 4.Department of Clinical Sciences, College of Veterinary MedicineNorth Carolina State UniversityRaleighUSA
  5. 5.Center for Comparative Medicine and Translational ResearchNorth Carolina State UniversityRaleighUSA
  6. 6.Cancer Genetics Program, Lineberger Comprehensive Cancer CenterUniversity of North CarolinaChapel HillUSA
  7. 7.Department of PathobiologyUniversity of GuelphGuelphCanada
  8. 8.Department of PediatricsUniversity of UtahSalt Lake CityUSA
  9. 9.Department of Oncological Sciences, Center for Children’s Cancer Research, Huntsman Cancer InstituteUniversity of UtahSalt Lake CityUSA

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