Mutational analysis of beta-catenin gene in Japanese ovarian carcinomas: frequent mutations in endometrioid carcinomas.
To investigate the contribution of the beta-catenin gene to the development of ovarian carcinomas, mutational analysis of exon 3 of the beta-catenin gene was conducted. We analyzed 61 primary ovarian carcinomas, consisting of 49 non-endometrioid-type and 12 endometrioid-type tumors, for genetic alteration of the beta-catenin gene. Five carcinomas showed beta-catenin mutations (S37C, T41I, T41A), including 4 (33%) of 12 endometrioid-type tumors and 1 (14%) of 7 mucinous-type tumors. All of these mutations altered at the serine/threonine residues that are potential sites of GSK3-beta phosphorylation. We detected no carcinomas with interstitial deletion involving exon 3 of beta-catenin. Furthermore, we immunohistochemically studied 27 of the 61 ovarian carcinomas. Both nuclear and cytoplasmic beta-catenin expressions were demonstrated in 4 of the 27 ovarian carcinomas for which tissue samples were available for examination. All 4 cases exhibited mutations in exon 3 of beta-catenin, including a mucinous carcinoma. Our results suggested that beta-catenin gene mutation at potential GSK3-beta phosphorylation sites results in accumulation of beta-catenin protein within the cells and its translocation to nuclei. Accumulated beta-catenin protein may be involved in the development of endometrioid-type ovarian carcinomas, and some mucinous-type ovarian carcinomas.
Sagae
S
S
Department of Obstetrics and Gynecology, Cancer Research Institute, Sapporo Medical University School of Medicine, Hokkaido. sagaes@sapmed.ac.jp
Kobayashi
K
K
Nishioka
Y
Y
Sugimura
M
M
Ishioka
S
S
Nagata
M
M
Terasawa
K
K
Tokino
T
T
Kudo
R
R
D000328:Adult; D018269:Carcinoma, Endometrioid / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D015894:Genome, Human; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin