[Epigenetic inactivation of microRNA genes in mammary carcinoma]

@article{citeulike:2805456, abstract = {AIMS: This study addresses the question whether microRNA genes are affected by aberrant hypermethylation and subsequent transcriptional repression in human breast cancer. METHODS: All known human microRNA genes were screened for the association with CpG islands using different algorithms. Methylation status of candidate genes was assessed in a panel of breast cancer cell lines, various normal tissue samples and primary breast cancer specimen using COBRA, bisulfite sequencing and pyrosequencing. Transcriptional silencing was measured by real-time RT-PCR. The effect of demethylation on microRNA gene expression was analysed in breast cancer cell lines after treatment with the DNMT inhibitor 5'-deoxy-2-azacytidine. RESULTS: Aberrant hypermethylation was shown for mir-9-1, mir-124a3, mir-148, mir-152, and mir-663 in 34-86\% of cases in a series of 71 primary human breast cancer specimens. miRNA gene hypermethylation correlated strongly with methylation of known tumour suppressor genes (p = 0.003). After treatment of various breast cancer cell lines with the demethylating agent 5-aza-2'deoxycytidine, reduction of mir-9-1 gene methylation and concomitant reactivation of expression could be observed. For the mir-9-1 gene, which is already hypermethylated in preinvasive intraductal lesions, a good correlation between quantitative methylation level and reduction of expression could be demonstrated in a subset of primary human breast cancer specimen (r = 0.8). CONCLUSIONS: In addition to deletion and mutation, microRNA genes are also affected by aberrant hypermethylation in human breast cancer. This epigenetic inactivation is frequent and occurs early during breast cancer progression.}, address = {Institut f\"{u}r Pathologie, Medizinische Hochschule Hannover, Hannover.}, author = {Lehmann, U. and Hasemeier, B. and R\"{o}mermann, D. and M\"{u}ller, M. and L\"{a}nger, F. and Kreipe, H. }, citeulike-article-id = {2805456}, issn = {0070-4113}, journal = {Verhandlungen der Deutschen Gesellschaft f\"{u}r Pathologie}, keywords = {cancer, epigenetics, microrna\_regulation}, pages = {214--220}, posted-at = {2008-05-16 16:24:09}, priority = {2}, title = {[Epigenetic inactivation of microRNA genes in mammary carcinoma]}, url = {http://view.ncbi.nlm.nih.gov/pubmed/18314617}, volume = {91}, year = {2007} }

TY - JOUR ID - citeulike:2805456 L3 - citeulike-article-id:2805456 TI - [Epigenetic inactivation of microRNA genes in mammary carcinoma] JF - Verhandlungen der Deutschen Gesellschaft für Pathologie VL - 91 SP - 214 EP - 220 AD - Institut für Pathologie, Medizinische Hochschule Hannover, Hannover. SN - 0070-4113 N2 - AIMS: This study addresses the question whether microRNA genes are affected by aberrant hypermethylation and subsequent transcriptional repression in human breast cancer. METHODS: All known human microRNA genes were screened for the association with CpG islands using different algorithms. Methylation status of candidate genes was assessed in a panel of breast cancer cell lines, various normal tissue samples and primary breast cancer specimen using COBRA, bisulfite sequencing and pyrosequencing. Transcriptional silencing was measured by real-time RT-PCR. The effect of demethylation on microRNA gene expression was analysed in breast cancer cell lines after treatment with the DNMT inhibitor 5'-deoxy-2-azacytidine. RESULTS: Aberrant hypermethylation was shown for mir-9-1, mir-124a3, mir-148, mir-152, and mir-663 in 34-86% of cases in a series of 71 primary human breast cancer specimens. miRNA gene hypermethylation correlated strongly with methylation of known tumour suppressor genes (p = 0.003). After treatment of various breast cancer cell lines with the demethylating agent 5-aza-2'deoxycytidine, reduction of mir-9-1 gene methylation and concomitant reactivation of expression could be observed. For the mir-9-1 gene, which is already hypermethylated in preinvasive intraductal lesions, a good correlation between quantitative methylation level and reduction of expression could be demonstrated in a subset of primary human breast cancer specimen (r = 0.8). CONCLUSIONS: In addition to deletion and mutation, microRNA genes are also affected by aberrant hypermethylation in human breast cancer. This epigenetic inactivation is frequent and occurs early during breast cancer progression. KW - cancer KW - epigenetics KW - microrna_regulation AU - Lehmann, U AU - Hasemeier, B AU - Römermann, D AU - Müller, M AU - Länger, F AU - Kreipe, H PY - 2007/// UR - http://view.ncbi.nlm.nih.gov/pubmed/18314617 ER -