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MYO18B , a candidate tumor suppressor gene at chromosome 22q12.1, deleted, mutated, and methylated in human lung cancer

2002; National Academy of Sciences; Volume: 99; Issue: 19 Linguagem: Inglês

10.1073/pnas.192445899

1091-6490

Michiho Nishioka, Takashi Kohno, Masachika Tani, Nozomu Yanaihara, Yoshio Tomizawa, Ayaka Otsuka, Shigeru Sasaki, Keiko Kobayashi, Toshiro Niki, Arafumi Maeshima, Yoshitaka Sekido, John D. Minna, Saburo Sone, Jun Yokota,

Genetics and Neurodevelopmental Disorders

Loss of heterozygosity on chromosome 22q has been detected in approximately 60% of advanced nonsmall cell lung carcinoma (NSCLC) as well as small cell lung carcinoma (SCLC), suggesting the presence of a tumor suppressor gene on 22q that is involved in lung cancer progression. Here, we isolated a myosin family gene, MYO18B , located at chromosome 22q12.1 and found that it is frequently deleted, mutated, and hypermethylated in lung cancers. Somatic MYO18B mutations were detected in 19% (14/75) of lung cancer cell lines and 13% (6/46) of primary lung cancers of both SCLC and NSCLC types. MYO18B expression was reduced in 88% (30/34) of NSCLC and 47% (8/17) of SCLC cell lines. Its expression was restored by treatment with 5-aza-2′-deoxycytidine in 11 of 14 cell lines with reduced MYO18B expression, and the promoter CpG island of the MYO18B gene was methylated in 17% (8/47) of lung cancer cell lines and 35% (14/40) of primary lung cancers. Furthermore, restoration of MYO18B expression in lung carcinoma cells suppressed anchorage-independent growth. These results indicate that the MYO18B gene is a strong candidate for a novel tumor suppressor gene whose inactivation is involved in lung cancer progression.