Influence of genetic background on tumor karyotypes: evidence for breed-associated cytogenetic aberrations in canine appendicular osteosarcoma.
Recurrent chromosomal aberrations in solid tumors can reveal the genetic pathways involved in the evolution of a malignancy and in some cases predict biological behavior. However, the role of individual genetic backgrounds in shaping karyotypes of sporadic tumors is unknown. The genetic structure of purebred dog breeds, coupled with their susceptibility to spontaneous cancers, provides a robust model with which to address this question. We tested the hypothesis that there is an association between breed and the distribution of genomic copy number imbalances in naturally occurring canine tumors through assessment of a cohort of Golden Retrievers and Rottweilers diagnosed with spontaneous appendicular osteosarcoma. Our findings reveal significant correlations between breed and tumor karyotypes that are independent of gender, age at diagnosis, and histological classification. These data indicate for the first time that individual genetic backgrounds, as defined by breed in dogs, influence tumor karyotypes in a cancer with extensive genomic instability.
Thomas
Rachael
R
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.|Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC 27606, USA.
Wang
Huixia J
HJ
Department of Statistics, College of Agriculture and Life Sciences, North Carolina State University, Raleigh, NC 27695, USA.
Tsai
Pei-Chien
PC
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Langford
Cordelia F
CF
Microarray Facility, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Fosmire
Susan P
SP
Integrated Department of Immunology, University of Colorado, Denver, CO 80214, USA.
Jubala
Cristan M
CM
Integrated Department of Immunology, University of Colorado, Denver, CO 80214, USA.
Getzy
David M
DM
Idexx Veterinary Services, Broomfield, CO 80020, USA.
Cutter
Gary R
GR
Department of Biostatistics, University of Alabama Birmingham, Birmingham, AL 35294, USA.
Modiano
Jaime F
JF
Integrated Department of Immunology, University of Colorado, Denver, CO 80214, USA.|University of Colorado Cancer Center, Aurora, CO 80045, USA.|Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, MN 55108, USA.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Breen
Matthew
M
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.|Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC 27606, USA.