Abstract | OBJECTIVE: To evaluate aberrations of the p53 tumor suppressor gene in naturally developing tumors in dogs. SAMPLE POPULATION: PROCEDURE: Aberrations of the p53 gene in these tumor tissues were examined by reverse transcriptase-polymerase chain reaction and single-strand conformation polymorphism analysis, using 3 fragments that covered the entire open reading frame of the canine p53 gene, followed by nucleotide sequencing of the abnormal bands. RESULTS: Point mutations, deletions, and insertions resulting in a number of amino acid substitutions of wild-type p53 were detected in 7 of the 15 tumor specimens from dogs with malignant lymphoma, monocytic leukemia, rhabdomyosarcoma, colon cancer, and osteosarcoma. Of these 7 dogs, 2 had aberrations of the p53 gene on both alleles, whereas 5 had aberrations of the p53 gene on 1 allele and concurrently lacked the wild-type p53 transcript. Many of the aberrations of the p53 gene detected in these tumors were located in the transactivation, DNA binding, and oligomerization domains. CONCLUSIONS AND CLINICAL RELEVANCE: Various naturally developing tumors in dogs often have inactivation of the p53 tumor suppressor gene, which may be 1 of the multiple step-wise genetic changes during tumorigenesis. This study indicates that p53 gene can be a target for gene therapy for tumors in dogs.
|
Authors | A Setoguchi, T Sakai, M Okuda, K Minehata, M Yazawa, T Ishizaka, T Watari, R Nishimura, N Sasaki, A Hasegawa, H Tsujimoto |
Journal | American journal of veterinary research
(Am J Vet Res)
Vol. 62
Issue 3
Pg. 433-9
(Mar 2001)
ISSN: 0002-9645 [Print] United States |
PMID | 11277210
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
|
Topics |
- Animals
- Base Sequence
- Blotting, Southern
- DNA, Neoplasm
(genetics)
- Dog Diseases
(genetics)
- Dogs
- Gene Deletion
- Genes, p53
(genetics)
- Molecular Sequence Data
- Neoplasms
(genetics, veterinary)
- Point Mutation
- Polymorphism, Single-Stranded Conformational
- Reverse Transcriptase Polymerase Chain Reaction
(veterinary)
- Sequence Analysis, DNA
|