Aberrations of the p53 tumor suppressor gene in various tumors in dogs

Objective-To evaluate aberrations of the p53 tumor suppressor gene in natur ally developing tumors in dogs. Sample Population-Tumor specimens from 15 dogs with various tumors, includi ng malignant lymphoma (7 dogs), monocytic leukemia (1), mammary gland adeno ma (1), mammary gland benign mixed tumor (1), rhabdomyosarcoma (1), colon c ancer (1), and osteosarcoma (3). Procedure-Aberrations of the p53 gene in these tumor tissues were examined by reverse transcriptase-polymerase chain reaction and single-strand confor mation polymorphism analysis, using 3 fragments that covered the entire ope n reading frame of the canine p53 gene, followed by nucleotide sequencing o f 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 tum or specimens from dogs with malignant lymphoma, monocytic leukemia, rhabdom yosarcoma, colon cancer, and osteosarcoma. Of these 7 dogs, 2 had aberratio ns of the p53 gene on both alleles, whereas 5 had aberrations of the p53 ge ne on 1 allele and concurrently lacked the wild-type p53 transcript. Many o f 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 d ogs often have inactivation of the p53 tumor suppressor gene, which may be 1 of the multiple step-wise genetic changes during tumorigenesis. This stud y indicates that p53 gene can be a target for gene therapy for tumors in do gs.