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.
Yanaihara
Nozomu
N
Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
Nishioka
Michiho
M
Kohno
Takashi
T
Otsuka
Ayaka
A
Okamoto
Aikou
A
Ochiai
Kazunori
K
Tanaka
Tadao
T
Yokota
Jun
J
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