Chromosome Research

, 17:987

Microarray-based cytogenetic profiling reveals recurrent and subtype-associated genomic copy number aberrations in feline sarcomas

  • Rachael Thomas
  • Victor E. Valli
  • Peter Ellis
  • Jerold Bell
  • Elinor K. Karlsson
  • John Cullen
  • Kerstin Lindblad-Toh
  • Cordelia F. Langford
  • Matthew Breen
Article

DOI: 10.1007/s10577-009-9096-0

Cite this article as:
Thomas, R., Valli, V.E., Ellis, P. et al. Chromosome Res (2009) 17: 987. doi:10.1007/s10577-009-9096-0

Abstract

Injection-site-associated sarcomas (ISAS), commonly arising at the site of routine vaccine administration, afflict as many as 22,000 domestic cats annually in the USA. These tumors are typically more aggressive and prone to recurrence than spontaneous sarcomas (non-ISAS), generally receiving a poorer long-term prognosis and warranting a more aggressive therapeutic approach. Although certain clinical and histological factors are highly suggestive of ISAS, timely diagnosis and optimal clinical management may be hindered by the absence of definitive markers that can distinguish between tumors with underlying injection-related etiology and their spontaneous counterpart. Specific nonrandom chromosome copy number aberrations (CNAs) have been associated with the clinical behavior of a vast spectrum of human tumors, providing an extensive resource of potential diagnostic and prognostic biomarkers. Although similar principles are now being applied with great success in other species, their relevance to feline molecular oncology has not yet been investigated in any detail. We report the construction of a genomic microarray platform for detection of recurrent CNAs in feline tumors through cytogenetic assignment of 210 large-insert DNA clones selected at intervals of ∼15 Mb from the feline genome sequence assembly. Microarray-based profiling of 19 ISAS and 27 non-ISAS cases identified an extensive range of genomic imbalances that were highly recurrent throughout the combined panel of 46 sarcomas. Deletions of two specific regions were significantly associated with the non-ISAS phenotype. Further characterization of these regions may ultimately permit molecular distinction between ISAS and non-ISAS, as a tool for predicting tumor behavior and prognosis, as well as refining means for therapeutic intervention.

Keywords

microarraycomparative genomic hybridization (CGH)felinesarcomachromosome

Abbreviations

BAC

Bacterial artificial chromosome

BLAST

Basic Local Alignment Search Tool

BLAT

BLAST-like alignment tool

CNA

Copy number aberration

DSH/DMH/DLH

Domestic short/medium/long hair

FBS

Fetal bovine serum

FCA

Felis catus

FeLV

Feline leukemia virus

FFPE

Formalin-fixed paraffin-embedded

FISH

Fluorescence in situ hybridization

H&E

Hematoxylin and eosin

ISAS

Injection-site-associated sarcoma

Mb

Megabase

NCBI

National Center for Biotechnology Information

RPCI

Roswell Park Cancer Institute

UCSC

University of California Santa Cruz

Supplementary material

10577_2009_9096_MOESM1_ESM.pdf (180 kb)
S1Signalment and aCGH data for all sarcoma cases analyzed (n = 46). The breed, age, and gender of each case are shown at the top of the chart, along with the anatomical location of the tumor. ISAS cases are listed to the left, and non-ISAS cases to the right. The first two columns indicate the chromosome and megabase location of arrayed BAC clones, which are listed in genomic order. Colored cells indicate the copy number status at each locus in each tumor case, based on the tumor DNA/reference DNA fluorescence intensity (red cells indicates genomic loss, test/reference ≤ 0.85:1; green cells indicates genomic gain, test/reference ≥ 1.15:1; yellow cells indicates genomic balance). M male, F female, DSH domestic short hair, DMH domestic medium hair, DLH domestic long hair (PDF 180 kb)

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Rachael Thomas
    • 1
    • 2
  • Victor E. Valli
    • 3
  • Peter Ellis
    • 4
  • Jerold Bell
    • 5
  • Elinor K. Karlsson
    • 6
    • 7
  • John Cullen
    • 8
  • Kerstin Lindblad-Toh
    • 6
    • 9
  • Cordelia F. Langford
    • 4
  • Matthew Breen
    • 1
    • 2
    • 10
  1. 1.Department of Molecular Biomedical Sciences, College of Veterinary MedicineNorth Carolina State UniversityRaleighUSA
  2. 2.Center for Comparative Medicine and Translational ResearchNorth Carolina State UniversityRaleighUSA
  3. 3.VDx Veterinary DiagnosticsDavisUSA
  4. 4.Microarray Facility, The Wellcome Trust Sanger InstituteWellcome Trust Genome CampusCambridgeUK
  5. 5.Department of Clinical SciencesTufts Cummings School of Veterinary MedicineGraftonUSA
  6. 6.Broad Institute of Harvard and MITCambridgeUSA
  7. 7.FAS Center for Systems BiologyHarvard UniversityCambridgeUSA
  8. 8.Department of Population Health and Pathobiology, College of Veterinary MedicineNorth Carolina State UniversityRaleighUSA
  9. 9.Department of Medical Biochemistry and MicrobiologyUppsala UniversityUppsalaSweden
  10. 10.Cancer Genetics ProgramUNC Lineberger Comprehensive Cancer CenterChapel HillUSA