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Allelic imbalance in chromosome band 18q21 and SMAD4 mutations in ovarian cancers

✍ Scribed by Satoshi Takakura; Aikou Okamoto; Misato Saito; Takaomi Yasuhara; Hideo Shinozaki; Seiji Isonishi; Tomoaki Yoshimura; Yasuyuki Ohtake; Kazunori Ochiai; Tadao Tanaka

Publisher: John Wiley and Sons
Year: 1999
Tongue: English
Weight: 179 KB
Volume: 24
Category: Article
ISSN: 1045-2257
DOI: 10.1002/(sici)1098-2264(199903)24:3<264::aid-gcc12>3.0.co;2-y

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✦ Synopsis

Recently, three candidate tumor suppressor genes, SMAD2 (MADR2/JV18-1), SMAD4 (DPC4), and DCC, were identified in chromosome band 18q21. We examined allelic imbalance (AI) in 18q21 using six polymorphic microsatellite markers in 38 primary ovarian cancers and four ovarian borderline tumors. AI at one or more loci was detected in 15 of 37 (41%) informative ovarian cancers and in none of the four borderline tumors. Frequent AI was detected at the D18S46 (31%) and D18S474 (36%) loci, which were adjacent to the SMAD4 gene, and at the D18S69 (33%) locus, which was telomeric to the DCC gene. Therefore, we searched for mutations of the SMAD4 gene in 42 primary tumors and eight cell lines by PCR-SSCP and sequencing analyses. Missense mutations were detected in two ovarian tumors and three ovarian cancer cell lines, whereas silent mutation was detected in a primary ovarian cancer. These results suggest that there are at least two tumor suppressor genes on chromosome arm 18q and that SMAD4 is of importance in ovarian tumorigenesis.

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