title: Influence of genetic background on tumor karyotypes: evidence for breed-associated cytogenetic aberrations in canine appendicular osteosarcoma.
abstract: 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.
authors.affiliation: 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.
authors.forename: Rachael
authors.initials: R
authors.lastname: Thomas
authors.affiliation: Department of Statistics, College of Agriculture and Life Sciences, North Carolina State University, Raleigh, NC 27695, USA.
authors.forename: Huixia J
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
authors.forename: Pei-Chien
authors.initials: PC
authors.lastname: Tsai
authors.affiliation: Microarray Facility, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Cordelia F
authors.initials: CF
authors.lastname: Langford
authors.affiliation: Integrated Department of Immunology, University of Colorado, Denver, CO 80214, USA.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Fosmire
authors.affiliation: Integrated Department of Immunology, University of Colorado, Denver, CO 80214, USA.
authors.forename: Cristan M
authors.initials: CM
authors.lastname: Jubala
authors.affiliation: Idexx Veterinary Services, Broomfield, CO 80020, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Getzy
authors.affiliation: Department of Biostatistics, University of Alabama Birmingham, Birmingham, AL 35294, USA.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Cutter
authors.affiliation: 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.
authors.forename: Jaime F
authors.initials: JF
authors.lastname: Modiano
authors.affiliation: 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.
authors.forename: Matthew
authors.initials: M
authors.lastname: Breen