Involvement of p53 gene mutations in human endometrial carcinomas.
Mutations in the p53 gene are associated with a wide variety of human malignancies. Point mutation in one allele and loss of the remaining one generally lead to inactivation of p53 protein. A high frequency of allelic losses corresponding to the 17p13.3 region that contained the p53 gene sequence was also noted in human endometrial carcinoma. Thus, in order to confirm involvement of the p53 gene in endometrial carcinogenesis, we searched for nucleotide sequence change in this gene in 42 endometrial carcinomas that had been subjected to previous LOH analyses. Using the polymerase-chain-reaction-single-strand conformation polymorphism (PCR-SSCP) method, we detected p53 gene mutations in 4 specimens. Two adenocarcinomas with allelic loss on 17p contained a mutant p53 gene in the allele that was retained. One specimen with a p53 gene mutation contained a 17q deletion but was uninformative for LOH on 17p. p53 gene mutation was also noted in the remaining stage-I carcinoma, though the 17p deletion was not detected in the previous LOH examination. However, 5 specimens with the LOH on 17p retained the wild-type p53 gene. In the remaining 33 specimens, both alleles of p53 gene seemed to be normal. The mutations observed in 2 specimens (cases 10 and 24), involving C-to-T and T-to-G substitutions, were located in a highly conserved region. However, the mutations identified in the remaining 2 cases (29 and 35) were at regions positioned outside conserved stretches.
Honda
T
T
Department of Reproductive Physiology and Endocrinology, Kyushu University, Beppu, Japan.
Kato
H
H
Imamura
T
T
Gima
T
T
Nishida
J
J
Sasaki
M
M
Hoshi
K
K
Sato
A
A
Wake
N
N
D000230:Adenocarcinoma / Q000235:genetics*; D000483:Alleles; D001483:Base Sequence; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000502:physiology; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004277:DNA, Single-Stranded / Q000032:analysis / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D017354:Point Mutation / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics
D004273:DNA, Neoplasm; D004277:DNA, Single-Stranded