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General assessment of copy number variation in normal and tumor tissues of the domestic dog (Canis lupus familiaris)

  • Animal Genetics ∙ Original Paper
  • Published:
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Abstract

In recent years, characterization of a copy number variation (CNV) of the genomic DNA has provided evidence for the relationship of this type of genetic variation with the occurrence of a broad spectrum of diseases, including cancer lesions. Copy number variants (CNVs) also occur in the genomes of healthy individuals as a result of abnormal recombination processes in germ cells and have a hereditary character contributing to the natural genetic diversity. Recent image analysis methods and advanced computational techniques allow for identification of CNVs using SNPs genotyping microarrays based on the analysis of signal intensity observed for markers located in the specific genomic regions. In this study we used CanineHD BeadChip assay (Illumina) to identify both natural and cancer-induced CNVs in the genomes of different dog breeds and in different cancer types occurring in this species. The obtained results showed that structural aberrations are a common phenomenon arising during a tumor progression and are more complex and widespread in tumors of mesenchymal tissue origin than in epithelial tissue originating tumors. The tumor derived CNVs, in comparison to healthy samples, were characterized by larger sizes of regions, higher number of amplifications, and in some cases encompassed genes with potential effect on tumor progression.

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References

  • Alvarez CE, Akey JM (2012) Copy number variation in the domestic dog. Mamm Genome 23:144–163

    Article  PubMed  Google Scholar 

  • Attiyeh EF, Diskin SJ, Attiyeh MA, Mossé YP, Hou C, Jackson EM, Kim C, Glessner J, Hakonarson H, Biegel JA, Maris JM (2009) Genomic copy number determination in cancer cells from single nucleotide polymorphism microarrays based on quantitative genotyping corrected for aneuploidy. Genome Res 19:276–283

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bae JS, Cheong HS, Kim LH, NamGung S, Park TJ, Chun JY, Kim JY, Pasaje CF, Lee JS, Shin HD (2010) Identification of copy number variations and common deletion polymorphisms in cattle. BMC Genomics 11:232

    Article  PubMed Central  PubMed  Google Scholar 

  • Baylin SB, Esteller M, Rountree MR, Bachman KE, Schuebel K, Herman JG (2001) Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet 10:687–692

    Article  CAS  PubMed  Google Scholar 

  • Berglund J, Nevalainen EM, Molin AM, Perloski M, The LUPA Consortium, André C, Zody MC, Sharpe T, Hitte C, Lindblad-Toh K, Lohi H, Webster MT (2012) Novel origins of copy number variation in the dog genome. Genome Biol 13:R73

    Article  PubMed Central  PubMed  Google Scholar 

  • Chen WK, Swartz JD, Rush LJ, Alvarez CE (2009) Mapping DNA structural variation in dogs. Genome Res 19:500–509

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Demichelis F, Setlur SR, Banerjee S, Chakravarty D, Chen JY, Chen CX, Huang J, Beltran H, Oldridge DA, Kitabayashi N, Stenzel B, Schaefer G, Horninger W, Bektic J, Chinnaiyan AM, Goldenberg S, Siddiqui J, Regan MM, Kearney M, Soong TD, Rickman DS, Elemento O, Wei JT, Scherr DS, Sanda MA, Bartsch G, Lee C, Klocker H, Rubin MA (2012) Identification of functionally active, low frequency copy number variants at 15q21.3 and 12q21.31 associated with prostate cancer risk. Proc Natl Acad Sci U S A 109:6686–6691

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Diskin SJ, Li M, Hou C, Yang S, Glessner J, Hakonarson H, Bucan M, Maris JM, Wang K (2008) Adjustment of genomic waves in signal intensities from whole-genome SNP genotyping platforms. Nucleic Acids Res 36:e126

    Article  PubMed Central  PubMed  Google Scholar 

  • Egenvall A, Bonnett BN, Ohagen P, Olson P, Hedhammar A, von Euler H (2005) Incidence of and survival after mammary tumors in a population of over 80,000 insured female dogs in Sweden from 1995 to 2002. Prev Vet Med 69:109–127

    Article  PubMed  Google Scholar 

  • Garnis C, Buys TP, Lam WL (2004) Genetic alteration and gene expression modulation during cancer progression. Mol Cancer 3:9

    Article  PubMed Central  PubMed  Google Scholar 

  • Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O’Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G et al (2007) Patterns of somatic mutation in human cancer genomes. Nature 446:153–158

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Henrichsen CN, Chaignat E, Reymond A (2009) Copy number variants, diseases and gene expression. Hum Mol Genet 18:R1–R8

    Article  CAS  PubMed  Google Scholar 

  • Higgins ME, Claremont M, Major JE, Sander C, Lash AE (2007) CancerGenes: a gene selection resource for cancer genome projects. Nucleic Acids Res 35:D721–D726

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Jiang L, Jiang J, Yang J, Liu X, Wang J, Wang H, Ding X, Liu J, Zhang Q (2013) Genome-wide detection of copy number variations using high-dens. BMC Genomics 14:131. doi:10.1186/1471-2164-14-131.ity

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Krajcovic M, Overholtzer M (2012) Mechanisms of ploidy increase in human cancers: a new role for cell cannibalism. Cancer Res 72:1596–1601

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • LaFramboise T, Weir BA, Zhao X, Beroukhim R, Li C, Harrington D, Sellers WR, Meyerson M (2005) Allele-specific amplification in cancer revealed by SNP array analysis. PLoS Comput Biol 1:e65

    Article  PubMed Central  PubMed  Google Scholar 

  • Lindblad-Toh K, Tanenbaum DM, Daly MJ, Winchester E, Lui WO, Villapakkam A, Stanton SE, Larsson C, Hudson TJ, Johnson BE, Lander ES, Meyerson M (2000) Loss-of-heterozygosity analysis of small-cell lung carcinomas using single-nucleotide polymorphism arrays. Nat Biotechnol 18:1001–1005

    Article  CAS  PubMed  Google Scholar 

  • Mardis ER, Wilson RK (2009) Cancer genome sequencing: a review. Hum Mol Genet 18:R163–R168

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Marenne G, Rodríguez-Santiago B, Closas MG, Pérez-Jurado L, Rothman N, Rico D, Pita G, Pisano DG, Kogevinas M, Silverman DT, Valencia A, Real FX, Chanock SJ, Génin E, Malats N (2011) Assessment of copy number variation using the Illumina Infinium 1M SNP-array: a comparison of methodological approaches in the Spanish Bladder Cancer/EPICURO study. Hum Mutat 32:240–248

    Article  PubMed Central  PubMed  Google Scholar 

  • Meyerson M, Gabriel S, Getz G (2010) Advances in understanding cancer genomes through second-generation sequencing. Nat Rev Genet 11:685–696

    Article  CAS  PubMed  Google Scholar 

  • Nicholas TJ, Cheng Z, Ventura M, Mealey K, Eichler EE, Akey JM (2009) The genomic architecture of segmental duplications and associated copy number variants in dogs. Genome Res 19:491–499

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nicholas TJ, Baker C, Eichler EE, Akey JM (2011) A high-resolution integrated map of copy number polymorphisms within and between breeds of the modern domesticated dog. BMC Genomics 12:414

    Article  PubMed Central  PubMed  Google Scholar 

  • Rivera P, von Euler H (2011) Molecular biological aspects on canine and human mammary tumors. Vet Pathol 48:132–146

    Article  CAS  PubMed  Google Scholar 

  • Schrider DR, Hahn MW (2010) Gene copy-number polymorphism in nature. Proc R Soc B 277:3213–3221

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ślaska B, Grzybowska-Szatkowska L, Bugno-Poniewierska M, Surdyka M, Śmiech A (2013) Nuclear and mitochondrial DNA mutation in human and canine tumors. Medycyna Weterynaryjna 69:195-202

    Google Scholar 

  • Taylor BS, Barretina J, Socci ND, DeCarolis P, Ladanyi M et al (2008) Functional copy-number alterations in cancer. PLoS ONE 3:e3179

    Article  PubMed Central  PubMed  Google Scholar 

  • The Cancer Genome Atlas Research Network (2012) Comprehensive genomic characterization of squamous cell lung cancers. Nature 489:519–525

    Article  PubMed Central  Google Scholar 

  • Thomas PD, Campbell MJ, Kejariwal A, Mi H, Karlak B, Daverman R, Diemer K, Muruganujan A, Narechania A (2003) PANTHER: a library of protein families and subfamilies indexed by function. Genome Res 13:2129–2141

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tran LM, Zhang B, Zhang Z, Zhang C, Xie T, Lamb JR, Dai H, Schadt EE, Zhu J (2011) Inferring causal genomic alterations in breast cancer using gene expression data. BMC Syst Biol 5:121

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yuan X, Yu G, Hou X, IeM S, Clarke R, Zhang J, Hoffman EP, Wang RR, Zhang Z, Wang Y (2012) Genome-wide identification of significant aberrations in cancer genome. BMC Genomics 13:342

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhao X, Li C, Paez JG, Chin K, Janne PA, Chen TH, Girard L, Minna J, Christiani D, Leo C, Gray JW, Sellers WR, Meyerson M (2004) An integrated view of copy number and allelic alterations in the cancer genome using single nucleotide polymorphism arrays. Cancer Res 64:3060–3071

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Genomics, National Research Institute of Animal Production, Krakowska 1, 32-083, Balice n. Krakow, Poland

    Artur Gurgul, Ewelina Semik, Klaudia Pawlina, Tomasz Ząbek, Igor Jasielczuk & Monika Bugno-Poniewierska

  2. Department of Animal Breeding and Genetics, National Research Institute of Animal Production, Krakowska 1, 32-083, Balice n. Krakow, Poland

    Kacper Żukowski

  3. Department of Biological Bases of Animal Production, Faculty of Animal Breeding Biology, University of Life Sciences in Lublin, Akademicka 13, 20-950, Lublin, Poland

    Brygida Ślaska

Authors
  1. Artur Gurgul
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  2. Kacper Żukowski
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  3. Brygida Ślaska
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  4. Ewelina Semik
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  5. Klaudia Pawlina
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  6. Tomasz Ząbek
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  7. Igor Jasielczuk
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  8. Monika Bugno-Poniewierska
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Correspondence to Artur Gurgul.

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Gurgul, A., Żukowski, K., Ślaska, B. et al. General assessment of copy number variation in normal and tumor tissues of the domestic dog (Canis lupus familiaris). J Appl Genetics 55, 353–363 (2014). https://doi.org/10.1007/s13353-014-0201-5

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  • DOI: https://doi.org/10.1007/s13353-014-0201-5

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