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Somatic alterations of the p53 tumor suppressor gene in vaccine-associated feline sarcoma

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  • 1 Department of Veterinary PathoBiology, College of Veterinary Medicine, Academic Health Center, University of Minnesota, Saint Paul, MN 55108.
  • | 2 Department of Veterinary PathoBiology, College of Veterinary Medicine, Academic Health Center, University of Minnesota, Saint Paul, MN 55108.
  • | 3 BioMedical Genomics Center, Academic Health Center, University of Minnesota, Saint Paul, MN 55108

Abstract

Objective—To determine somatic alterations in p53 in vaccine-associated feline sarcoma (VAFS).

Animals—27 domestic shorthair cats undergoing first surgical treatment for primary VAFS with no history of chemotherapy or γ radiation.

Procedures—Sequence analysis was performed on the genomic sequence of p53 (between exons 5 through 9) from tumor and blood samples obtained from the cats. Cats were monitored for 3 years and disease-free intervals and survival times calculated.

Results—Eight single nucleotide polymorphisms were detected within the genomic sequence of p53, with 20 of 27 cats (74%) having heterozygosity at ≥ 1 polymorphic site. Somatic loss of heterozygosity at p53 was detected in the primary tumors of 12 of these 20 (60%) cats. Such allelic deletion was significantly associated with rapid tumor recurrence and reduced overall survival. Point mutations were rare, occurring in 3 of 27 primary tumors. The finding of malignant cells in the surgical margins was significantly associated with disease recurrence, but clear margins (with no detectable malignant cells) were not predictive of positive outcome.

Conclusions and Clinical Relevancep53 status is an indicator of postsurgical recurrence and overall survival in cats with VAFS. Careful follow-up is important in treating vaccine-site tumors containing allelic deletion of p53, whereas aggressive surgical treatment may be sufficient to control primary vaccination site tumors without the allelic loss.

Abstract

Objective—To determine somatic alterations in p53 in vaccine-associated feline sarcoma (VAFS).

Animals—27 domestic shorthair cats undergoing first surgical treatment for primary VAFS with no history of chemotherapy or γ radiation.

Procedures—Sequence analysis was performed on the genomic sequence of p53 (between exons 5 through 9) from tumor and blood samples obtained from the cats. Cats were monitored for 3 years and disease-free intervals and survival times calculated.

Results—Eight single nucleotide polymorphisms were detected within the genomic sequence of p53, with 20 of 27 cats (74%) having heterozygosity at ≥ 1 polymorphic site. Somatic loss of heterozygosity at p53 was detected in the primary tumors of 12 of these 20 (60%) cats. Such allelic deletion was significantly associated with rapid tumor recurrence and reduced overall survival. Point mutations were rare, occurring in 3 of 27 primary tumors. The finding of malignant cells in the surgical margins was significantly associated with disease recurrence, but clear margins (with no detectable malignant cells) were not predictive of positive outcome.

Conclusions and Clinical Relevancep53 status is an indicator of postsurgical recurrence and overall survival in cats with VAFS. Careful follow-up is important in treating vaccine-site tumors containing allelic deletion of p53, whereas aggressive surgical treatment may be sufficient to control primary vaccination site tumors without the allelic loss.

Contributor Notes

Drs. Banerji and Kanjilal's present address is Department of Medicine, Medical School, University of Minnesota, 1500 Gortner Avenue, Saint Paul, MN 55108.

Supported in part by the Vaccine-Associated Feline Sarcoma Task Force and the Morris Animal Foundation.

The authors thank Dr. Kaisa Kivilaid for statistical evaluations and Xia Li for technical assistance.

Address correspondence to Dr. Kanjilal.