Dominant-negative mutation of p53 tumor suppressor gene in endometrial carcinoma.
BACKGROUND
It has been suggested that mutation of the TP53 tumor suppressor gene is involved in endometrial carcinogenesis. However, the status of p53 function in endometrial cancers has not yet been investigated in detail.


METHODS
We surveyed inactivating p53 mutations in endometrial carcinomas using the yeast p53 functional assay, which can evaluate the transcriptional activity of p53 in vivo in yeast. To the detected p53 mutants, we also applied a transdominance assay, which assesses the dominant-negative property of mutants.


RESULTS
Of 23 endometrial carcinomas, 9 tumors (39.1%) were found to harbor p53 mutations. Only 1 of the 6 mutants in 18 endometrioid-type tumors showed dominant-negative capacity. In contrast to the endometrioid-type tumor, all 3 mutations in 5 serous-type tumors (R273H, 9-bp deletion in codons 240-243, and R248W) showed dominant-negative capacity and presented in a homozygous state in the tumors, indicating a complete functional inactivation.


CONCLUSIONS
Although this study included a relatively small number of cases and therefore is a preliminary study, these results suggest that the dominant-negative mutation of the TP53 gene is related to serous adenocarcinoma. The role of the dominant-negative status of p53 mutants in endometrial carcinogenesis and progression of this disease should be further investigated.
Sakuragi
N
N
Department of Obstetrics and Gynecology, Hokkaido University, Sapporo, 060-8638, Japan. sakuragi@tara.med.hokudai.ac.jp
Hirai
A
A
Tada
M
M
Yamada
H
H
Yamamoto
R
R
Fujimoto
S
S
Moriuchi
T
T
D000328:Adult; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000235:genetics; D018284:Cystadenocarcinoma, Serous / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D020868:Gene Silencing; D005799:Genes, Dominant; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics; D015533:Transcriptional Activation