Methylomic analysis identifies frequent DNA methylation of Zinc Finger protein 582 (ZNF582) in cervical neoplasms

Rui Lan Huang; Cheng Chang Chang; Po Hsuan Su; Yu Chih Chen; Yu Ping Liao; Hui Chen Wang; Yi Te Yo; Tai Kuang Chao; Hsuan Cheng Huang; Ching Yu Lin; Tang Yuan Chu; Hung Cheng Lai

doi:10.1371/journal.pone.0041060

Methylomic analysis identifies frequent DNA methylation of Zinc Finger protein 582 (ZNF582) in cervical neoplasms

Rui Lan Huang, Cheng Chang Chang, Po Hsuan Su, Yu Chih Chen, Yu Ping Liao, Hui Chen Wang, Yi Te Yo, Tai Kuang Chao, Hsuan Cheng Huang, Ching Yu Lin, Tang Yuan Chu, Hung Cheng Lai

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Despite of the trend that the application of DNA methylation as a biomarker for cancer detection is promising, clinically applicable genes are few. Therefore, we looked for novel hypermethylated genes for cervical cancer screening. Methods and Findings: At the discovery phase, we analyzed the methylation profiles of human cervical carcinomas and normal cervixes by methylated DNA immunoprecipitation coupled to promoter tiling arrays (MeDIP-on-chip). Methylation-specific PCR (MSP), quantitative MSP and bisulfite sequencing were used to verify the methylation status in cancer tissues and cervical scrapings from patients with different severities. Immunohistochemical staining of a cervical tissue microarray was used to confirm protein expression. We narrowed to three candidate genes: DBC1, PDE8B, and ZNF582; their methylation frequencies in tumors were 93%, 29%, and 100%, respectively. At the pre-validation phase, the methylation frequency of DBC1 and ZNF582 in cervical scraping correlated significantly with disease severity in an independent cohort (n = 330, both P

Original language	English
Article number	e41060
Journal	PLoS ONE
Volume	7
Issue number	7
DOIs	https://doi.org/10.1371/journal.pone.0041060
Publication status	Published - Jul 16 2012

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title = "Methylomic analysis identifies frequent DNA methylation of Zinc Finger protein 582 (ZNF582) in cervical neoplasms",

abstract = "Background: Despite of the trend that the application of DNA methylation as a biomarker for cancer detection is promising, clinically applicable genes are few. Therefore, we looked for novel hypermethylated genes for cervical cancer screening. Methods and Findings: At the discovery phase, we analyzed the methylation profiles of human cervical carcinomas and normal cervixes by methylated DNA immunoprecipitation coupled to promoter tiling arrays (MeDIP-on-chip). Methylation-specific PCR (MSP), quantitative MSP and bisulfite sequencing were used to verify the methylation status in cancer tissues and cervical scrapings from patients with different severities. Immunohistochemical staining of a cervical tissue microarray was used to confirm protein expression. We narrowed to three candidate genes: DBC1, PDE8B, and ZNF582; their methylation frequencies in tumors were 93%, 29%, and 100%, respectively. At the pre-validation phase, the methylation frequency of DBC1 and ZNF582 in cervical scraping correlated significantly with disease severity in an independent cohort (n = 330, both P",

author = "Huang, {Rui Lan} and Chang, {Cheng Chang} and Su, {Po Hsuan} and Chen, {Yu Chih} and Liao, {Yu Ping} and Wang, {Hui Chen} and Yo, {Yi Te} and Chao, {Tai Kuang} and Huang, {Hsuan Cheng} and Lin, {Ching Yu} and Chu, {Tang Yuan} and Lai, {Hung Cheng}",

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AU - Huang, Rui Lan

AU - Chang, Cheng Chang

AU - Su, Po Hsuan

AU - Chen, Yu Chih

AU - Liao, Yu Ping

AU - Wang, Hui Chen

AU - Yo, Yi Te

AU - Chao, Tai Kuang

AU - Huang, Hsuan Cheng

AU - Lin, Ching Yu

AU - Chu, Tang Yuan

AU - Lai, Hung Cheng

PY - 2012/7/16

Y1 - 2012/7/16

N2 - Background: Despite of the trend that the application of DNA methylation as a biomarker for cancer detection is promising, clinically applicable genes are few. Therefore, we looked for novel hypermethylated genes for cervical cancer screening. Methods and Findings: At the discovery phase, we analyzed the methylation profiles of human cervical carcinomas and normal cervixes by methylated DNA immunoprecipitation coupled to promoter tiling arrays (MeDIP-on-chip). Methylation-specific PCR (MSP), quantitative MSP and bisulfite sequencing were used to verify the methylation status in cancer tissues and cervical scrapings from patients with different severities. Immunohistochemical staining of a cervical tissue microarray was used to confirm protein expression. We narrowed to three candidate genes: DBC1, PDE8B, and ZNF582; their methylation frequencies in tumors were 93%, 29%, and 100%, respectively. At the pre-validation phase, the methylation frequency of DBC1 and ZNF582 in cervical scraping correlated significantly with disease severity in an independent cohort (n = 330, both P

AB - Background: Despite of the trend that the application of DNA methylation as a biomarker for cancer detection is promising, clinically applicable genes are few. Therefore, we looked for novel hypermethylated genes for cervical cancer screening. Methods and Findings: At the discovery phase, we analyzed the methylation profiles of human cervical carcinomas and normal cervixes by methylated DNA immunoprecipitation coupled to promoter tiling arrays (MeDIP-on-chip). Methylation-specific PCR (MSP), quantitative MSP and bisulfite sequencing were used to verify the methylation status in cancer tissues and cervical scrapings from patients with different severities. Immunohistochemical staining of a cervical tissue microarray was used to confirm protein expression. We narrowed to three candidate genes: DBC1, PDE8B, and ZNF582; their methylation frequencies in tumors were 93%, 29%, and 100%, respectively. At the pre-validation phase, the methylation frequency of DBC1 and ZNF582 in cervical scraping correlated significantly with disease severity in an independent cohort (n = 330, both P

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Methylomic analysis identifies frequent DNA methylation of Zinc Finger protein 582 (ZNF582) in cervical neoplasms

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