Reduced expression of MYO18B, a candidate tumor-suppressor gene on chromosome arm 22q, in ovarian cancer.
Allelic imbalance on chromosome arm 22q has been detected in 50-70% of ovarian cancers, suggesting the presence of a tumor-suppressor gene on this chromosome arm that is involved in ovarian carcinogenesis. Recently, we isolated a candidate tumor-suppressor gene, MYO18B, at 22q12.1, which is deleted, mutated and hypermethylated in approximately 50% of lung cancers. In our study, we analyzed genetic and epigenetic alterations of the MYO18B gene in ovarian cancers. Missense MYO18B mutations were detected in 1 of 4 (25%) ovarian cancer cell lines and in 1 of 17 (5.9%) primary ovarian cancers. MYO18B expression was reduced in all 4 ovarian cancer cell lines and in 12 of 17 (71%) of primary ovarian cancers. MYO18B expression was restored by treatment with 5-aza-2'-deoxycytidine and/or trichostatin A in 3 of 4 cell lines with reduced MYO18B expression, and hypermethylation of the promoter CpG island for MYO18B was observed in 2 of these 3 cell lines. Its hypermethylation was also observed in 2 of 15 (13%) primary ovarian cancers. Thus, it was indicated that MYO18B expression is reduced in a considerable fraction of ovarian cancers by several mechanisms, including hypermethylation, while the MYO18B gene is mutated in a small subset of ovarian cancers. The present results suggest that MYO18B alterations, including both epigenetic and genetic alterations, play an important role in ovarian carcinogenesis.
Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
Nozomu
N
Yanaihara
Michiho
M
Nishioka
Takashi
T
Kohno
Ayaka
A
Otsuka
Aikou
A
Okamoto
Kazunori
K
Ochiai
Tadao
T
Tanaka
Jun
J
Yokota
D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D018282:Cystadenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D000077209:Decitabine; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D020125:Mutation, Missense / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D006877:Hydroxamic Acids; C012589:trichostatin A; D000077209:Decitabine; D018995:Myosin Heavy Chains; D001374:Azacitidine