Chromosome Research

, Volume 23, Issue 4, pp 681–708

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
Article

DOI: 10.1007/s10577-015-9475-7

Cite this article as:
Roode, S.C., Rotroff, D., Avery, A.C. et al. Chromosome Res (2015) 23: 681. doi:10.1007/s10577-015-9475-7

Abstract

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.

Keywords

Leukemia Canine Chromosome Comparative genomic hybridization Comparative genomics 

Abbreviations

ALL

Acute lymphoblastic leukemia

AML

Acute myeloid leukemia

BAC

Bacterial artificial chromosome

CFA

Canis familiaris

CLL

Chronic lymphocytic leukemia

CML

Chronic myeloid leukemia

CMML

Chronic myelomonocytic leukemia

CMoL

Chronic monocytic leukemia

CNA

Copy number aberration

CNV

Copy number variant

FISH

Fluorescence in situ hybridization

GISTIC

Genomic Identification of Significant Targets in Cancer

HSA

Homo sapiens

LSA

Lymphosarcoma

oaCGH

Oligonucleotide array comparative genomic hybridization

SNP

Single nucleotide polymorphism

TZL

T zone lymphoma

WBC

White blood cell

Supplementary material

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