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The canine p53 gene is subject to somatic mutations in thypoid carcinoma
P Devilee1, I S Van Leeuwen, A Voesten
1Department of Pathology, University of Leiden, The Netherlands.
Abstract:
In many different types of tumors in man and mouse, p53 is the tumor suppressor gene most frequently affected by a combination of somatic mutation and loss of the wildtype allele. In order to develop a molecular tool to study the genetic evolution of tumors in the dog, we have cloned an evolutionary conserved part of the canine homologue of p53. The isolated genomic segment, 534 bp in length, contains the 3' half of exon 5, the complete exon 6 and the 5' half of exon 7, as well as the intronic intervening sequences. The gene organization of this segment shows strong homology to that published earlier for a number of other species, including man, mouse, and Xenopus laevis. This conservation is apparent at the DNA sequence level, as well as at the deduced aminoacid sequence level. mRNA expression can be detected at low levels in normal tissues with increased mitotic activity, and in the Madin-Darby canine kidney cell line. A-->G T transversion was found in 1 out of 23 investigated primary thyroid carcinomas at a position corresponding to codon 174 in the human p53, and was predicted to give rise to an aminoacid substitution in the protein. These results suggest that p53 plays a role in the development of malignancy in the dog, in a way comparable to that in man.
Insights
Researchers cloned a conserved segment of the canine p53 tumor suppressor gene to study canine cancer evolution. This gene shows similar function and mutation patterns to human p53, suggesting its role in canine malignancy.
Area of Science:
- Molecular Biology
- Oncology
- Comparative Genomics
Background:
- The p53 tumor suppressor gene is frequently altered in human and mouse cancers.
- Understanding canine p53 is crucial for developing molecular tools to study canine tumor evolution.
Purpose of the Study:
- To clone and characterize a conserved segment of the canine p53 homologue.
- To investigate the potential role of p53 in canine malignancy.
Main Methods:
- Cloning of a 534 bp genomic segment of canine p53 (exons 5-7 and intervening introns).
- Sequence analysis to assess homology with other species.
- mRNA expression analysis in normal tissues and cell lines.
- Mutation screening in canine thyroid carcinomas.
Main Results:
- The cloned canine p53 segment shows strong homology to human, mouse, and Xenopus laevis.
- Conserved gene organization at both DNA and amino acid levels was observed.
- Canine p53 mRNA is expressed in normal tissues and kidney cell lines.
- A specific mutation (A-->G T transversion) was identified in one thyroid carcinoma, predicting an amino acid substitution.
Conclusions:
- The cloned canine p53 segment provides a molecular tool for studying canine tumor genetics.
- p53 appears to play a role in canine cancer development, similar to its role in humans.