A commonly deleted region in ovarian cancer on chromosome 19p13.3, not including the OAZ1 gene.
Antizyme is a negative regulator of cellular polyamines. The gene for antizyme (OAZ1) is mapped to 19p13.3, where frequent allelic imbalance (AI) is observed in ovarian cancer. The potential role of antizyme 1 in ovarian carcinogenesis was addressed in this study. Mutations of the OAZ1 gene, including the entire coding region and associated promoter region, were examined in 50 primary ovarian tumors and 8 ovarian cancer cell lines by PCR-SSCP and sequencing analyses. A missense mutation in exon 1 and a nucleotide change at the 3'-UTR were detected in an ovarian cancer cell line and its derivative cisplatin resistant cell line. No somatic mutation was detected in primary ovarian tumors, although 7 polymorphic sites were identified. AI of the OAZ1 gene was detected in 7 of 30 informative cases of primary ovarian cancer (23%). Subsequent multiplex fluorescent microsatellite analysis at 7 loci on 19p and at 4 loci on 19q in 50 primary ovarian tumors revealed a commonly deleted region, approximately 4.7 Mb, between the D19S424 and D19S884 loci on 19p13.3 in the vicinity of the OAZ1 locus. The most frequent AI was observed at D19S216 (50%). These results suggest that one or more tumor suppressor genes other than OAZ1 exist near the D19S216 locus on 19p13.3.
Yanaihara
Nozomu
N
Department of Obstetrics and Gynecology, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-846, Japan.
Okamoto
Aikou
A
Matsufuji
Senya
S
D045744:Cell Line, Tumor; D002888:Chromosomes, Human, Pair 19; D002945:Cisplatin / Q000494:pharmacology; D017931:DNA Primers / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005091:Exons; D005260:Female; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006801:Humans; D018895:Microsatellite Repeats; D008957:Models, Genetic; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D011073:Polyamines / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D011073:Polyamines; D011506:Proteins; C031017:ornithine decarboxylase antizyme; D002945:Cisplatin