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

National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 10/2002; 99(19):12269-74. DOI: 10.1073/pnas.192445899
Source: PubMed

ABSTRACT 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.

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Available from: John Minna, Jan 01, 2015
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    • "Cytoplasmic in myoblasts, diffuse nuclear in myocytes (Salamon et al. 2003) Tumor suppressor (Nishioka et al. 2002) "
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    • "We previously isolated a novel unconventional myosin, MYO18B, from a homozygously deleted region at chromosome 22q12.1 in a human lung cancer cell line (Nishioka et al. 2002). Inactivation of this gene by genetic and/or epigenetic alterations in human cancer cells suggests that the MYO18B gene functions as a tumor suppressor in human carcinogenesis (Nishioka et al. 2002; Tani et al. 2004; Yanaihara et al. 2004; Nakano et al. 2005). Like other myosins, MYO18B has a myosin head motor domain with an ATP-binding motif and a GPA actin-binding motif. "
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    • "+ More frequently methylated in tumors . (NSCLC) [229] MYOD1 myogenic differentiation 1 [11p15] ++ More frequently methylated in tumors. [50] PAX5 paired box gene 5 (B-cell lineage specific activator) [9p13] + + + 50–60% methylated in adenocarcinoma ; frequency similar to adjcent non-tumor lung. "
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