Mutation of Canine Tumor Suppressor Gene p53 in a Mammary Gland Adenocarcinoma and a Malignant Mast Cell Tumor

개의 유선암종과 악성 비만세포 종양에서 발생한 종양억제 유전자 p53의 변이

  • Lee, Chung-ho (Department of Veterinary Surgery, College of Veterinary Medicine, Seoul National University) ;
  • Kweon, Oh-kyeong (Department of Veterinary Surgery, College of Veterinary Medicine, Seoul National University)
  • Published : 2002.06.01

Abstract

To identify mutations in exons 5 to 8 of the p53 tumor suppressor gene, we have analysed in 12 spontaneous canine tumors. In a malignant mast cell tumor, a 1 base pair alteration AGT $\longrightarrow$AGC (silent point mutation, serine) in codon 249 in exon 8 was detected. And the mammary gland adenocarcinoma was found to have a mis-sense point mutation (CCT $\longrightarrow$ TCT) in codon 285 in exon 8.

개에서 자연적으로 발생한 12예의 종양에 대해, 종양 억제 유전자 p53의 변이와의 관계를 확인해 보았다. 종양조직에서 일반적인 방법으로 DNA를 추출하여, PCR 기법으로 p53을 증폭하여 염기서열을 확인한 결과, 개의 유선암종 예에서 exon 8의 codon 285에서 CCT $\longrightarrow$ TCT (proline $\longrightarrow$ serine)로 점변이 된 것이 확인되었다. 또한 악성 비만세포 종양 예에서도 exon 8의 codon 249에서 AGT $\longrightarrow$AGC로 점변이 된 것이 확인되었으나 silent point mutation (serine)으로 판명되었다. 이상의 결과를 토대로 개의 유선암종과 악성 비만세포 종양에서 종양억제 유전자 p53의 변이가 확인되었으며, 이는 종양의 형성과 관련된 p53의 역할이나 종양의 치료 및 예후 판정에 p53 을 활용하는 연구의 초석이 되리라 사료되며, 차후 이 유전자에 대한 광범위한 연구가 지속되어야 하리라 생각된다.

Keywords

References

  1. Breast Cancer Res Treat v.50 Genomic organization of the canine p53 gene and its mutational status in canine mammary neopolasia Chu LL;Rutteman GR;Kong JM;Ghahremani M;Schmeing M;Misdorp W;van Garderen E;Pelletier J https://doi.org/10.1023/A:1006010526813
  2. Anticancer Res v.14 The canine p53 gene is subject to somatic mutations in thyroid carcinoma Devilee P;Van Leeuwen IS;Voesten A;Rutteman GR;Vos JH;Cornelisse CJ
  3. Carcinogenesis v.19 Mutation of the p53 tumor suppressot gene in spontaneously occurring osteosarcomas of the dog Johnson AS;Couto CG;Weghorst CM https://doi.org/10.1093/carcin/19.1.213
  4. Cancer Lett v.92 Sequence analysis of canine p53 in the region of exons 3-8 Kraegel SA;Pazzi KA;Madewell BR https://doi.org/10.1016/0304-3835(95)03779-V
  5. Am J Vet Res v.59 Cytogenetic alterations in eight mammary tumors and tumor-suppressor gene p53 mutation in one mammary tumor form dogs Mayr B;Dressler A;Reifinger M;Feil C
  6. Vet Res Commun v.23 Novel canine tumour suppressor gene p53 mutations in cases of skin and mammary neoplasms Mayr B;Reifinger M;Alton K https://doi.org/10.1023/A:1006314903272
  7. The Vet J v.155 Polymorphisms in feline tumour suppressor gene p53. Mutations in an osteodarcoma and a Mammary Carcinoma Mayr B;Reifinger M;Loupal G https://doi.org/10.1016/S1090-0233(98)80044-0
  8. Vet Res Commun v.21 Canine tumour suppressor gene p53-mutation in a case of adenoma of circumanal glands Mayr B;Schaffner W;Botto I;Reifinger M;Loupal G https://doi.org/10.1023/A:1005820607258
  9. Br Vet J v.150 Sequence of an exon of the canine p53 gene-mutation in a papilloma Mayr B;Schellander K;Schleger W;Reifinger M https://doi.org/10.1016/S0007-1935(05)80099-5
  10. Trends Genet v.5 An efficient saltchloroform extraction of DNA from blood and tissues Mullenbach R;Lagoda PJ;Welter C
  11. Am J Vet Res v.62 Aberrations of the p53 tumor suppressor gene in various tumors in dogs Setoguchi A;Sakai T;Okuda M;Minehata K;Yazawa M;Ishizaka T;Watari T;Nishimura R;Sasaki N;Hasegawa A;Tsujimoto H https://doi.org/10.2460/ajvr.2001.62.433
  12. Cancer Res v.48 Chromosomal reorganization for the expression of recessive mutation of retinoblastoma susceptibility gene in the development of osteosarcoma Toguchida J;Ishizaki K;Sasaki M;Ikenaga M;Sugimoto M;Kotoura Y;Yamamuro T
  13. Anticancer Res v.16 P53 mutations in mammary tumor cell lines and corresponding tumor tissues in the dog Van Leeuwen IS;Hellmen E;Cornelisse CJ;Van den Burgh B;Rutteman GR
  14. Oncogene v.16 Isolation of canine p53 cDNA and detailed characterization of the full length canine p53 protein Veldhoen N;Milner J https://doi.org/10.1038/sj.onc.1201863
  15. Oncogene v.16 Mutations of the p53 gene in canine lymphoma and evidence for germ line p53 mutations in the dog Veldhoen N;Stewart J;Brown R;Milner J https://doi.org/10.1038/sj.onc.1201489
  16. Br J Cancer v.81 Identification of tumour-associated and germ line p53 mutation in canine mammary cancer Veldhoen N;Watterson J;Brash M;Milner J https://doi.org/10.1038/sj.bjc.6690709