The canine p53 gene is subject to somatic mutations in thypoid carcinoma.
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.
Department of Pathology, University of Leiden, The Netherlands.
P
P
Devilee
I S
IS
Van Leeuwen
A
A
Voesten
G R
GR
Rutteman
J H
JH
Vos
C J
CJ
Cornelisse
D000595:Amino Acid Sequence; D000782:Aneuploidy; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004285:Dogs; D005091:Exons; D016158:Genes, p53; D015698:Genomic Library; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D013964:Thyroid Neoplasms / Q000235:genetics*
D018076:DNA, Complementary; D004273:DNA, Neoplasm; D012333:RNA, Messenger