caa a22 4500 606190600 CHVBK 20210128100856.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s10577-015-9475-7 doi (NATIONALLICENCE)springer-10.1007/s10577-015-9475-7 Genome-wide assessment of recurrent genomic imbalances in canine leukemia identifies evolutionarily conserved regions for subtype differentiation [Elektronische Daten] [Sarah Roode, Daniel Rotroff, Anne Avery, Steven Suter, Dorothee Bienzle, Joshua 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 ∼25Mb 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. Springer Science+Business Media Dordrecht, 2015 Leukemia nationallicence Canine nationallicence Chromosome nationallicence Comparative genomic hybridization nationallicence Comparative genomics nationallicence ALL : Acute lymphoblastic leukemia nationallicence AML : Acute myeloid leukemia nationallicence BAC : Bacterial artificial chromosome nationallicence CFA : Canis familiaris nationallicence CLL : Chronic lymphocytic leukemia nationallicence CML : Chronic myeloid leukemia nationallicence CMML : Chronic myelomonocytic leukemia nationallicence CMoL : Chronic monocytic leukemia nationallicence CNA : Copy number aberration nationallicence CNV : Copy number variant nationallicence FISH : Fluorescence in situ hybridization nationallicence GISTIC : Genomic Identification of Significant Targets in Cancer nationallicence HSA : Homo sapiens nationallicence LSA : Lymphosarcoma nationallicence oaCGH : Oligonucleotide array comparative genomic hybridization nationallicence SNP : Single nucleotide polymorphism nationallicence TZL : T zone lymphoma nationallicence WBC : White blood cell nationallicence Roode Sarah Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, 27607, Raleigh, NC, USA aut Rotroff Daniel Bioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, USA aut Avery Anne Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Science, Colorado State University, Fort Collins, CO, USA aut Suter Steven Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA aut Bienzle Dorothee Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada aut Schiffman Joshua Department of Pediatrics, University of Utah, Salt Lake City, UT, USA aut Motsinger-Reif Alison Bioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, USA aut Breen Matthew Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, 27607, Raleigh, NC, USA aut Chromosome Research Springer Netherlands 23/4(2015-12-01), 681-708 0967-3849 23:4<681 2015 23 10577 https://doi.org/10.1007/s10577-015-9475-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10577-015-9475-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Roode Sarah Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, 27607, Raleigh, NC, USA aut NATIONALLICENCE 700 1- Rotroff Daniel Bioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, USA aut NATIONALLICENCE 700 1- Avery Anne Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Science, Colorado State University, Fort Collins, CO, USA aut NATIONALLICENCE 700 1- Suter Steven Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA aut NATIONALLICENCE 700 1- Bienzle Dorothee Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada aut NATIONALLICENCE 700 1- Schiffman Joshua Department of Pediatrics, University of Utah, Salt Lake City, UT, USA aut NATIONALLICENCE 700 1- Motsinger-Reif Alison Bioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, USA aut NATIONALLICENCE 700 1- Breen Matthew Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, 27607, Raleigh, NC, USA aut NATIONALLICENCE 773 0- Chromosome Research Springer Netherlands 23/4(2015-12-01), 681-708 0967-3849 23:4<681 2015 23 10577