Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

British Journal of Cancer
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. british journal of cancer
  3. regular article
  4. article
Identification of tumour-associated and germ line p53 mutations in canine mammary cancer
Download PDF
Download PDF
  • Regular Article
  • Open access
  • Published: 10 September 1999

Identification of tumour-associated and germ line p53 mutations in canine mammary cancer

  • N Veldhoen1,
  • J Watterson1,
  • M Brash2 &
  • …
  • J Milner1 

British Journal of Cancer volume 81, pages 409–415 (1999)Cite this article

  • 1367 Accesses

  • 33 Citations

  • Metrics details

This article has been updated

Summary

Mutations of the tumour suppressor p53 gene are found in a number of spontaneous canine cancers and may contribute to increased cytogenetic alterations and tumour formation. Using reverse transcription and DNA amplification, we isolated p53 cDNA from normal and tumour tissue of ten canine mammary cancer patients. DNA sequencing identified p53 mutations in three of the ten patients. These included tumour-associated p53 gene mutations within exons 2 and 5 and a germ line deletion of exons 3 to 7. These results support a role for p53 inactivation in canine mammary tumour formation and breed predisposition to cancer. Such information could prove invaluable in the successful outbreeding of inherited predisposition to cancer in the dog. A putative polymorphism was also identified at codon 69 in exon 4 and we discuss the possibility that similar polymorphisms may be associated with human breast cancer.

Similar content being viewed by others

Canine tumor mutational burden is correlated with TP53 mutation across tumor types and breeds

Article Open access 03 August 2021

Analyses of canine cancer mutations and treatment outcomes using real-world clinico-genomics data of 2119 dogs

Article Open access 19 January 2023

PIK3CA is recurrently mutated in canine mammary tumors, similarly to in human mammary neoplasia

Article Open access 12 January 2023

Article PDF

Change history

  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  • Ara, S, Lee, PS, Hansen, MF & Saya, H (1990). Codon 72 polymorphism of the TP53 gene. Nucleic Acids Res 18: 4961.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berns, EM, Klijn, JG, Smid, M, van Staveren, IL, Look, MP, van Putten, WL & Foekens, JA (1996). TP53 and MYC gene alterations independently predict poor prognosis in breast cancer patients. Genes Chromosomes Cancer 16: 170–179.

    Article  CAS  PubMed  Google Scholar 

  • Béroud, C & Soussi, T (1998). p53 gene mutation: software and database. Nucleic Acids Res 26: 200–204.

    Article  PubMed  PubMed Central  Google Scholar 

  • Birch, JM, Blair, V, Kelsey, AM, Evans, DG, Harris, M, Tricker, KJ & Varley, JM (1998). Cancer phenotype correlates with constitutional TP53 genotype in families with the Li–Fraumeni syndrome. Oncogene 17: 1061–1068.

    Article  CAS  PubMed  Google Scholar 

  • Casey, G, Lopez, ME, Ramos, JC, Plummer, SJ, Arboleda, MJ, Shaughnessy, M, Karlan, B & Slamon, DJ (1996). DNA sequence analysis of exons 2 through 11 and immunohistochemical staining are required to detect all known p53 alterations in human malignancies. Oncogene 13: 1971–1981.

    CAS  PubMed  Google Scholar 

  • Chang, H, Benchimol, S, Minden, MD & Messner, HA (1994). Alterations of p53 and c-myc in the clonal evolution of malignant lymphoma. Blood 83: 452–459.

    CAS  PubMed  Google Scholar 

  • Chu, LL, Rutteman, GR, Kong, JMC, Ghahremani, M, Schmeing, M, Misdorp, W, van Garderen, E & Pelletier, J (1998). Genomic organization of the canine p53 gene and its mutational status in canine mammary neoplasia. Breast Cancer Res Treat 50: 11–25.

    Article  CAS  PubMed  Google Scholar 

  • Cook, A & Milner, J (1990). Evidence for allosteric variants of wild-type p53, a tumour suppressor protein. Br J Cancer 61: 548–552.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Devilee, P, van Leeuwen, IS, Voesten, A, Rutteman, GR, Vos, JH & Cornelisse, CJ (1994). The canine p53 gene is subject to somatic mutations in thyroid carcinoma. Anticancer Res 14: 2039–2046.

    CAS  PubMed  Google Scholar 

  • Faille, A, De Cremoux, P, Extra, JM, Linares, G, Espie, M, Bourstyn, E, De Rocquancourt, A, Giacchetti, S, Marty, M & Calvo, F (1994). p53 mutations and overexpression in locally advanced breast cancers. Br J Cancer 69: 1145–1150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gamble, J & Milner, J (1988). Evidence that immunological variants of p53 represent alternative protein conformations. Virology 162: 452–458.

    Article  CAS  PubMed  Google Scholar 

  • Gannon, JV, Greaves, R, Iggo, R & Lane, DP (1990). Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form. EMBO J 9: 1595–1602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glebov, OK, McKenzie, KE, White, CA & Sukumar, S (1994). Frequent p53 gene mutations and novel alleles in familial breast cancer. Cancer Res 54: 3703–3709.

    CAS  PubMed  Google Scholar 

  • Hainaut, P, Soussi, T, Shomer, B, Hollstein, M, Greenblatt, M, Hovig, E, Harris, CC & Montesano, R (1997). Database of p53 gene somatic mutations in human tumors and cell lines: updated compilation and future prospects. Nucleic Acids Res 25: 151–157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hartmann, A, Blaszyk, H, Kovach, JS & Sommer, SS (1997). The molecular epidemiology of p53 gene mutations in human breast cancer. Trends Genet 13: 27–33.

    Article  CAS  PubMed  Google Scholar 

  • Helland, Ã…, Langerød, A, Johnsen, H, Olsen, AO, Skovlund, E & Børresen-Dale, A-L (1998). p53 polymorphism and risk of cervical cancer. Nature 396: 530–531.

    Article  CAS  PubMed  Google Scholar 

  • Hirano, Y, Yamato, K & Tsuchida, N (1995). A temperature sensitive mutant of the human p53, Val138, arrests rat cell growth without induced expression of cip1/waf1/sdi1 after temperature shift-down. Oncogene 10: 1879–1885.

    CAS  PubMed  Google Scholar 

  • Huang, Y, Yin, J & Meltzer, SJ (1994). A unique p53 intragenic deletion flanked by short direct repeats results in loss of mRNA expression in a human esophageal carcinoma. Carcinogenesis 15: 1653–1655.

    Article  CAS  PubMed  Google Scholar 

  • Johnson, AS, Couto, CG & Weghorst, CM (1998). Mutation of the p53 tumor suppressor gene in spontaneously occurring osteosarcomas of the dog. Carcinogenesis 19: 213–217.

    Article  CAS  PubMed  Google Scholar 

  • Kussie, PH, Gorina, S, Marechal, V, Elenbaas, B, Moreau, J, Levine, AJ & Pavletich, N (1996). Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 274: 948–953.

    Article  CAS  PubMed  Google Scholar 

  • Lin, J, Wu, X, Chen, J, Chang, A & Levine, AJ (1995). Functions of the p53 protein in growth-regulation and tumor suppression. Cold Spring Harbor Symp Quant Biol 59: 215–223.

    Article  Google Scholar 

  • MacVean, DW, Monlux, AW, Anderson, PS Jr, Silberg, SL & Roszel, JF (1978). Frequency of canine and feline tumors in a defined population. Vet Pathol 15: 700–715.

    Article  CAS  PubMed  Google Scholar 

  • Malkin, D (1994). Germline p53 mutations and heritable cancer. Annu Rev Genet 28: 443–465.

    Article  CAS  PubMed  Google Scholar 

  • Martinez, J, Georgoff, I, Martinez, J & Levine, A (1991). Cellular localization and cell cycle regulation by a temperature-sensitive p53 protein. Genes Dev 5: 151–159.

    Article  CAS  PubMed  Google Scholar 

  • Mayr, B, Schellander, K, Schleger, W & Reifinger, M (1994). Sequence of an exon of the canine p53 gene-mutation in a papilloma. Br Vet J 150: 81–84.

    Article  CAS  PubMed  Google Scholar 

  • Mayr, B, Schaffner, W, Botto, I, Reifinger, M & Loupal, G (1997). Canine tumour suppressor gene p53-mutation in a case of adenoma of circumanal glands. Vet Res Comm 21: 369–373.

    Article  CAS  Google Scholar 

  • Mayr, B, Dressler, A, Reifinger, M & Feil, C (1998). Cytogenetic alterations in eight mammary tumors and tumor-suppressor gene p53 mutation in one mammary tumor from dogs. Am J Vet Res 59: 69–78.

    CAS  PubMed  Google Scholar 

  • Minaguchi, T, Kanamori, Y, Matsushima, M, Yoshikawa, H, Taketani, Y & Nakamura, Y (1998). No evidence of correlation between polymorphism at codon 72 of p53 and risk of cervical cancer in Japanese patients with human papillomavirus 16/18 infection. Cancer Res 58: 4585–4586.

    CAS  PubMed  Google Scholar 

  • Moll, UM, Riou, G & Levine, AJ (1992). Two distinct mechanisms alter p53 in breast cancer: mutation and nuclear exclusion. Proc Natl Acad Sci USA 89: 7262–7266.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Priester, WA & McKay, FW (1980). The occurrence of tumors in domestic animals. Natl Cancer Inst Monograph 54: 152–184.

    Google Scholar 

  • Rolley, N, Butcher, S & Milner, J (1995). Specific DNA binding by different classes of human p53 mutants. Oncogene 11: 763–770.

    CAS  PubMed  Google Scholar 

  • Rosenthal, AN, Ryan, A, Al-Jehani, RM, Storey, A, Harwood, CA & Jacobs, IJ (1998). p53 codon 72 polymorphism and risk of cervical cancer in UK. Lancet 352: 871–872.

    Article  CAS  PubMed  Google Scholar 

  • Seth, A, Palli, D, Mariano, JM, Metcalf, R, Venanzoni, M, Bianchi, S, Kottaridis, SD & Papas, TS (1994). P53 gene mutations in women with breast cancer and a previous history of benign breast disease. Eur J Cancer 30A: 808–812.

    Article  CAS  PubMed  Google Scholar 

  • Storey, A, Thomas, M, Kalita, A, Harwood, C, Gardiol, D, Mantovani, F, Breuer, J, Leigh, IM, Matlashewski, G & Banks, L (1998). Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature 393: 229–234.

    Article  CAS  PubMed  Google Scholar 

  • Strauss, BS (1997). Silent and multiple mutations in p53 and the question of the hypermutability of tumors. Carcinogenesis 18: 1445–1452.

    Article  CAS  PubMed  Google Scholar 

  • Sun, X-F, Johannsson, O, HÃ¥kansson, S, Sellberg, G, Nordenskjöld, B, Olsson, H & Borg, A (1996). A novel p53 germline alteration identified in a late onset breast cancer kindred. Oncogene 13: 407–411.

    CAS  PubMed  Google Scholar 

  • Tagawa, M, Murata, M & Kimura, H (1998). Prognostic value of mutations and germ line polymorphism of the p53 gene in non-small cell lung carcinoma: association with clinicopathological features. Cancer Lett 128: 93–99.

    Article  CAS  PubMed  Google Scholar 

  • Tornaletti, S & Pfeifer, GP (1995). Complete and tissue-independent methylation of CpG sites in the p53 gene: implications for mutations in human cancers. Oncogene 10: 1493–1499.

    CAS  PubMed  Google Scholar 

  • van Leeuwen, IS, Hellmen, E, Cornelisse, CJ, van den Burgh, B & Rutteman, GR (1996). P53 mutations in mammary tumor cell lines and corresponding tumor tissues in the dog. Anticancer Res 16: 3737–3744.

    CAS  PubMed  Google Scholar 

  • van Leeuwen, IS, Cornelisse, CJ, Misdorp, W, Goedegebuure, SA, Kirpensteijn, J & Rutteman, GR (1997). P53 gene mutations in osteosarcomas in the dog. Cancer Lett 111: 173–178.

    Article  CAS  PubMed  Google Scholar 

  • Veldhoen, N & Milner, J (1998). Isolation of canine p53 cDNA and detailed characterization of the full length canine p53 protein. Oncogene 16: 1077–1084.

    Article  CAS  PubMed  Google Scholar 

  • Veldhoen, N, Stewart, J, Brown, R & Milner, J (1998). Mutations of the p53 gene in canine lymphoma and evidence for germ line p53 mutations in the dog. Oncogene 16: 249–255.

    Article  CAS  PubMed  Google Scholar 

  • Venkatachalam, S, Shi, Y-P, Jones, SN, Vogel, H, Bradley, A, Pinkel, D & Donehower, LA (1998). Retention of wild-type p53 in tumors from p53 heterozygous mice: reduction of p53 dosage can promote cancer formation. EMBO J 17: 4657–4667.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wada, H, Asada, M, Nakazawa, S, Itoh, H, Kobayashi, Y, Inoue, T, Fukumuro, K, Chan, LC, Sugita, K, Hanada, R, Akuta, N, Kobayashi, N & Mizutani, S (1994). Clonal expansion of p53 mutant cells in leukemia progression in vitro. Leukemia 8: 53–59.

    CAS  PubMed  Google Scholar 

  • Yamato, K, Yamamoto, M, Hirano, Y & Tsuchida, N (1995). A human temperature-sensitive p53 mutant p53val-138: modulation of the cell cycle, viability and expression of p53-responsive genes. Oncogene 11: 1–6.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology, YCR P53 Research Group, University of York, York, YO10 5DD, UK

    N Veldhoen, J Watterson & J Milner

  2. Battle Flatts Veterinary Clinic, 38 Main Street, Stamford Bridge, York, YO4 1AB, UK

    M Brash

Authors
  1. N Veldhoen
    View author publications

    Search author on:PubMed Google Scholar

  2. J Watterson
    View author publications

    Search author on:PubMed Google Scholar

  3. M Brash
    View author publications

    Search author on:PubMed Google Scholar

  4. J Milner
    View author publications

    Search author on:PubMed Google Scholar

Additional information

Correspondence to: J Milner

Rights and permissions

From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

Reprints and permissions

About this article

Cite this article

Veldhoen, N., Watterson, J., Brash, M. et al. Identification of tumour-associated and germ line p53 mutations in canine mammary cancer. Br J Cancer 81, 409–415 (1999). https://doi.org/10.1038/sj.bjc.6690709

Download citation

  • Received: 10 December 1998

  • Revised: 23 March 1999

  • Accepted: 01 April 1999

  • Published: 10 September 1999

  • Issue date: 01 October 1999

  • DOI: https://doi.org/10.1038/sj.bjc.6690709

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • germline
  • DNA mutation
  • canine p53
  • mammary cancer

This article is cited by

  • Establishment of TP53-knockout canine cells using optimized CRIPSR/Cas9 vector system for canine cancer research

    • Kiyoung Eun
    • Min Gi Park
    • Hyunggee Kim

    BMC Biotechnology (2019)

  • The ESR1 gene is associated with risk for canine mammary tumours

    • Kaja Sverdrup Borge
    • Malin Melin
    • Frode Lingaas

    BMC Veterinary Research (2013)

Download PDF

Advertisement

Explore content

  • Research articles
  • Reviews & Analysis
  • News & Comment
  • Current issue
  • Collections
  • Follow us on Twitter
  • Sign up for alerts
  • RSS feed

About the journal

  • Journal Information
  • Open access publishing
  • About the Editors
  • Contact
  • Special Issues
  • For Advertisers
  • Subscribe

Publish with us

  • For Authors & Referees
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

British Journal of Cancer (Br J Cancer)

ISSN 1532-1827 (online)

ISSN 0007-0920 (print)

nature.com sitemap

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited