Hypermethylation of the large tumor suppressor genes in Japanese lung cancer
- PMID: 22966299
- PMCID: PMC3436364
- DOI: 10.3892/ol_00000054
Hypermethylation of the large tumor suppressor genes in Japanese lung cancer
Abstract
Large tumor suppressor (LATS) 1 and 2 are tumor suppressor genes implicated in the regulation of the cell cycle. The methylation statuses of the promoter regions of these genes were studied in Japanese lung cancers. The methylation statuses of the promoter regions of LATS1 and LATS2 were investigated by methylation-specific PCR. The findings were compared to clinicopathological features of lung cancer. Methylation-specific PCR showed that the LATS1 promoter region was hypermethylated in 95 out of 119 (79.8%) lung cancers. The methylation status of LATS1 was significantly associated with squamous histology (p=0.0267) and smoking status (never smoker vs. smoker; p=0.0399). LATS1-ummethylated patients harbored more EGFR mutations (p=0.0143). The LATS2 promoter region was hypermethylated in 160 out of 203 (78.8%) lung cancers. However, the methylation status had no association with the clinicopathological characteristics of the lung cancers cases. Both the LATS1 and LATS2 methylation statuses did not correlate with survival of lung cancer patients. Thus, the EGFR methylation status of the LATS genes has limited value in Japanese lung cancers.
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References
-
- Justice RW, Zilian O, Woods DF, Noll M, Bryant PJ. The Drosophila tumor suppressor gene warts encodes a homolog of human myotonic dystrophy kinase and is required for the control of cell shape and proliferation. Genes Dev. 1995;9:534–546. - PubMed
-
- Xu T, Wang W, Zhang S, Stewart RA, Yu W. Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. Development. 1995;121:1053–1063. - PubMed
-
- John MA, Tsao W, Fei X, et al. Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumors and pituitary dysfunction. Nat Genet. 1999;21:182–186. - PubMed
-
- Yang X, Li D, Chen W, Xu T. Human homologue of the Drosophila lats, LATS1, negatively regulates growth by inducing G2/M arrest or apoptosis. Oncogene. 2001;20:6516–6523. - PubMed
-
- Xia H, Qi H, Li Y, et al. LATS1 tumor suppressor regulates G2/M transition and apoptosis. Oncogene. 2001;21:1233–1241. - PubMed
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