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

Recently, three candidate tumor suppressor genes, SMAD2 (MADR2/JV18-1), SMA D4 (DPC4), and DCC, were identified in chromosome band 18q21. We examined a llelic imbalance (Al) in 18q21 using six polymorphic microsatellite markers in 38 primary ovarian cancers and four ovarian borderline tumors. Al at on e or more loci was detected in 15 of 37 (41%) informative ovarian cancers a nd in none of the four borderline tumors. Frequent Al was detected at the D 18S46 (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. Therefo re, we searched for mutations of the SMAD4 gene in 42 primary tumors and ei ght cell lines by PCR-SSCP and sequencing analyses. Missense mutations were detected in two ovarian tumors and three ovarian cancer cell lines, wherea s silent mutation was detected in a primary ovarian cancer. These results s uggest that there are at least two tumor suppressor genes on chromosome arm 18q and that SMAD4 is of importance in ovarian tumorigenesis. Genes Chromo somes Cancer 24:264-271, 1999. (C) 1999 Wiley-Liss, Inc.