Pharmacologic Unmasking of Epigenetically Silenced Genes in Breast Cancer Export

@article{citeulike:4072717, abstract = {Purpose: Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of various cancers including breast cancer. Many epigenetically inactivated genes involved in breast cancer development remain to be identified. Therefore, in this study we used a pharmacologic unmasking approach in breast cancer cell lines with 5-aza-2'-deoxycytidine (5-aza-dC) followed by microarray expression analysis to identify epigenetically inactivated genes in breast cancer. Experimental Design: Breast cancer cell lines were treated with 5-aza-dC followed by microarray analysis to identify epigenetically inactivated genes in breast cancer. We then used bisulfite DNA sequencing, conventional methylation-specific PCR, and quantitative fluorogenic real-time methylation-specific PCR to confirm cancer-specific methylation in novel genes. Results: Forty-nine genes were up-regulated in breast cancer cells lines after 5-aza-dC treatment, as determined by microarray analysis. Five genes (MAL, FKBP4, VGF, OGDHL, and KIF1A) showed cancer-specific methylation in breast tissues. Methylation of at least two was found at high frequency only in breast cancers (40 of 40) as compared with normal breast tissue (0 of 10; P < 0.0001, Fisher's exact test). Conclusions: This study identified new cancer-specific methylated genes to help elucidate the biology of breast cancer and as candidate diagnostic markers for the disease. 10.1158/1078-0432.CCR-08-1304}, author = {Ostrow, Kimberly L. and Park, Hannah L. and Hoque, Mohammad O. and Kim, Myoung S. and Liu, Junwei and Argani, Pedram and Westra, William and Criekinge, Wim V. and Sidransky, David}, citeulike-article-id = {4072717}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/1078-0432.CCR-08-1304}, citeulike-linkout-1 = {http://clincancerres.aacrjournals.org/cgi/content/abstract/15/4/1184?etoc}, day = {15}, doi = {10.1158/1078-0432.CCR-08-1304}, journal = {Clin Cancer Res}, keywords = {breast, cell, epigenetics, gene\_specific\_methylation}, month = {February}, number = {4}, pages = {1184--1191}, posted-at = {2009-02-20 01:29:26}, priority = {2}, title = {Pharmacologic Unmasking of Epigenetically Silenced Genes in Breast Cancer}, url = {http://dx.doi.org/10.1158/1078-0432.CCR-08-1304}, volume = {15}, year = {2009} }

TY - JOUR ID - citeulike:4072717 L3 - citeulike-article-id:4072717 N2 - Purpose: Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of various cancers including breast cancer. Many epigenetically inactivated genes involved in breast cancer development remain to be identified. Therefore, in this study we used a pharmacologic unmasking approach in breast cancer cell lines with 5-aza-2'-deoxycytidine (5-aza-dC) followed by microarray expression analysis to identify epigenetically inactivated genes in breast cancer. Experimental Design: Breast cancer cell lines were treated with 5-aza-dC followed by microarray analysis to identify epigenetically inactivated genes in breast cancer. We then used bisulfite DNA sequencing, conventional methylation-specific PCR, and quantitative fluorogenic real-time methylation-specific PCR to confirm cancer-specific methylation in novel genes. Results: Forty-nine genes were up-regulated in breast cancer cells lines after 5-aza-dC treatment, as determined by microarray analysis. Five genes (MAL, FKBP4, VGF, OGDHL, and KIF1A) showed cancer-specific methylation in breast tissues. Methylation of at least two was found at high frequency only in breast cancers (40 of 40) as compared with normal breast tissue (0 of 10; P < 0.0001, Fisher's exact test). Conclusions: This study identified new cancer-specific methylated genes to help elucidate the biology of breast cancer and as candidate diagnostic markers for the disease. 10.1158/1078-0432.CCR-08-1304 IS - 4 JF - Clin Cancer Res EP - 1191 TI - Pharmacologic Unmasking of Epigenetically Silenced Genes in Breast Cancer VL - 15 SP - 1184 KW - breast KW - cell KW - epigenetics KW - gene_specific_methylation AU - Ostrow, Kimberly AU - Park, Hannah AU - Hoque, Mohammad AU - Kim, Myoung AU - Liu, Junwei AU - Argani, Pedram AU - Westra, William AU - Criekinge, Wim AU - Sidransky, David PY - 2009/02/15/ UR - http://dx.doi.org/10.1158/1078-0432.CCR-08-1304 ER -