Aberrations of the p53 tumor suppressor gene in various tumors in dogs.
OBJECTIVE
To evaluate aberrations of the p53 tumor suppressor gene in naturally developing tumors in dogs.


METHODS
Tumor specimens from 15 dogs with various tumors, including malignant lymphoma (7 dogs), monocytic leukemia (1), mammary gland adenoma (1), mammary gland benign mixed tumor (1), rhabdomyosarcoma (1), colon cancer (1), and osteosarcoma (3).


METHODS
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
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.
Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Japan.
A
A
Setoguchi
T
T
Sakai
M
M
Okuda
K
K
Minehata
M
M
Yazawa
T
T
Ishizaka
T
T
Watari
R
R
Nishimura
N
N
Sasaki
A
A
Hasegawa
H
H
Tsujimoto
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D004273:DNA, Neoplasm / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D017353:Gene Deletion; D016158:Genes, p53 / Q000235:genetics*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics / Q000662:veterinary*; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D017422:Sequence Analysis, DNA
D004273:DNA, Neoplasm