Abstract
Earlier, methylation of a CpG island in the SEMA3B gene (3p21.31) was observed in cell lines of small-cell and non-small-cell lung carcinoma. According to NCBI (Build 36), that island belonged to intron 1 of the gene. Our study concerns the methylation of two CpG islands, promoter and intronic, in the SEMA3B gene in patients with clear cell renal cell carcinoma (RCC). Methylation-specific PCR and bisulfite sequencing revealed a high frequency of methylation in the promoter CpG island (34/61, 56%) and somewhat lower, in the intronic (17/48, 35%). A significant inverse correlation was found between the SEMA3B mRNA level and methylation of the promoter CpG island in RCC (P < 0.05 according to Fisher’s exact test). The intronic island showed no such correlation. Thus, we suggest that the methylation of the promoter CpG island contributes to the inactivation of the SEMA3B suppressor gene in RCC tissue.
References
Tomizawa Y., Sekido Y., Kondo M., et al. 2001. Inhibition of lung cancer cell growth and induction of apoptosis after reexpression of 3p21.3 candidate tumor suppressor gene SEMA3B. Proc. Natl. Acad. Sci. USA. 98, 13954–13959.
Tse C., Xiang R.H., Bracht T., Naylor S.L. 2002. Human Semaphorin 3B (SEMA3B) located at chromosome 3p21.3 suppresses tumor formation in an adenocarcinoma cell line. Cancer Res. 62, 542–546.
Kisselev L.L., Senchenko V.N., Oparina N.Yu., Braga E.A., Zabarovsky E.R. 2005. Tumor suppressor genes localized on the short arm of human chromosome 3. Mol. Meditsina. 3, 17–28.
Kuroki T., Trapasso F., Yendamuri S., et al. 2003. Allelic loss on chromosome 3p21.3 and promoter hypermethylation of Semaphorin 3B in non-small cell lung cancer. Cancer Res. 63, 3352–3355.
Ito M., Ito G., Kondo M., et al. 2005. Frequent inactivation of RASSF1A, BLU, and SEMA3B on 3p21.3 by promoter hypermethylation and allele loss in non-small cell lung cancer. Cancer Lett. 225, 131–139.
Pronina I.V., Loginov V.I., Prasolov V.S., et al. 2009. Changes in the level of SEMA3B gene expression in epithelial tumors. Mol. Biol. 43, 439–445.
Braga E.A., Loginov V.I., Klimova E.A., et al. 2006. Activation of RHOA transcription in epithelial tumors may be caused by gene amplification and/or demethylation of the promoter region. Mol. Biol. 40, 865–877.
Khodyrev D.S., Loginov V.I., Pronina I.V., et al. 2008. Methylation of promoter region of RAR-2 gene in renal cell, breast, and ovarian carcinomas. Genetika. 44, 1126–1132.
Herman J.G., Graff J.R., Myohanen S., et al. 1996. Methylation-specific PCR: A novel PCR assay for methylation status of CpG islands. Proc. Natl. Acad. Sci. USA. 93, 9821–9826.
Angeloni D. 2007. Molecular analysis of deletions in human chromosome 3p21 and the role of resident cancer genes in disease. Brief Funct. Genomic Proteomic. 6, 19–39.
Hesson L.B., Cooper W.N., Latif F. 2007. Evaluation of the 3p21.3 tumour-suppressor gene cluster. Oncogene. 26, 7283–7301.
Tischoff I., Markwarth A., Witzigmann H., et al. 2005. Allele loss and epigenetic inactivation of 3p21.3 in malignant liver tumors. Int. J. Cancer. 115, 684–689.
Nair P.N., McArdle L., Cornell J., et al. 2007. High-resolution analysis of 3p deletion in neuroblastoma and differential methylation of the SEMA3B tumor suppressor gene. Cancer Genet. Cytogenet. 174, 100–110.
Riquelme E., Tang M., Baez S., et al. 2007. Frequent epigenetic inactivation of chromosome 3p candidate tumor suppressor genes in gallbladder carcinoma. Cancer Lett. 250, 100–106.
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Original Russian Text © V.I. Loginov, D.S. Khodyrev, I.V. Pronina, A.V. Malyukova, T.P. Kazubskaya, V. D. Ermilova, R.F. Gar’kavtseva, E.R. Zabarovskii, E.A. Braga, 2009, published in Molekulyarnaya Biologiya, 2009, Vol. 43, No. 6, pp. 1088–1092.
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Loginov, V.I., Khodyrev, D.S., Pronina, I.V. et al. Two CpG islands in the SEMA3B gene: Methylation in clear cell renal cell carcinoma. Mol Biol 43, 1014–1018 (2009). https://doi.org/10.1134/S0026893309060156
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DOI: https://doi.org/10.1134/S0026893309060156