Aberrant Promoter Methylation and Tumor Suppressive Activity of the DFNA5 Gene in Colorectal Carcinoma
Oncogene (2008) 27, 3624–3634 & 2008 Nature Publishing Group All rights reserved 0950-9232/08 $30.00 www.nature.com/onc ORIGINAL ARTICLE Aberrant promoter methylation and tumor suppressive activity of the DFNA5 gene in colorectal carcinoma MS Kim1, X Chang1, K Yamashita1, JK Nagpal1, JH Baek2,GWu3, B Trink1, EA Ratovitski1, M Mori4 and D Sidransky1 1Department of Otolaryngology, Head and Neck Cancer Research Division, Johns Hopkins University, Baltimore, MD, USA; 2Department of Genetic Medicine, Institute of Cell Engineering, Johns Hopkins University, Baltimore, MD, USA; 3Karmanos Cancer Institute, Department of Pathology, Wayne State University, Detroit, MI, USA and 4Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Tsurumibaru, Beppu, Japan To identify novel methylated gene promoters, we com- Introduction pared differential RNA expression profiles of colorectal cancer (CRC) cell lines with or without treatment of Aberrant gene expression is a characteristic of human 5-aza-20-deoxycytidine (5-aza-dC). Out of 1776 genes cancers, and changes in DNA methylation status can that were initially ‘absent (that is, silenced)’ by gene have profound effects on the expression of genes. Tumor expression array analysis, we selected 163 genes that were suppressor genes (TSGs) display both genetic and increased after 5-aza-dC treatment in at least two of three epigenetic inactivation in human tumors, and the CRC cell lines. The microarray results were confirmed by transcriptional silencing of TSGs has established hy- Reverse Transcription–PCR, and CpG island of the gene permethylation as a common mechanism for loss of promoters were amplified and sequenced for examination TSG function in human cancer (Herman, 1999).
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