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

Asuka SetoguchiDepartment of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113- 8657, Japan.

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Tadashi SakaiDepartment of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113- 8657, Japan.

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Masaru OkudaDepartment of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113- 8657, Japan.

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Kenichi MinehataDepartment of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113- 8657, Japan.

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Mitsuhiro YazawaDepartment of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113- 8657, Japan.

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Tomomichi IshizakaDepartment of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113- 8657, Japan.

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Toshihiro WatariLaboratory of Comprehensive Veterinary Clinical Sciences, Nihon University School of Veterinary Medicine, Kanagawa 252-8510, Japan.

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Ryohei NishimuraDepartment of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113- 8657, Japan.

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Nobuo SasakiDepartment of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113- 8657, Japan.

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Atsuhiko HasegawaDepartment of Pathobiology, Nihon University School of Veterinary Medicine, Kanagawa 252-8510, Japan.

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Hajime TsujimotoDepartment of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113- 8657, Japan.

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Abstract

Objective—To evaluate aberrations of the p53 tumor suppressor gene in naturally developing tumors in dogs.

Sample Population—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).

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. (Am J Vet Res 2001;62:433–439)

Abstract

Objective—To evaluate aberrations of the p53 tumor suppressor gene in naturally developing tumors in dogs.

Sample Population—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).

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. (Am J Vet Res 2001;62:433–439)