Methylated B3GAT2 and ZNF793 Are Potential Detection Biomarkers for Barrett's Esophagus.
Title: | Methylated B3GAT2 and ZNF793 Are Potential Detection Biomarkers for Barrett's Esophagus. |
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Authors: | Ming Yu, O'Leary, Rachele M., Kaz, Andrew M., Morris, Shelli M., Carter, Kelly T., Chak, Amitabh, Chandar, Apoorva, Willis, Joseph E., Moinova, Helen R., Markowitz, Sanford D., Brenner, Dean E., Anandabapasathy, Sharmila, Westerhoff, Maria, Chao-Jen Wong, Shaheen, Nicholas J., Yanwen Chen, Barnholtz-Sloan, Jill S., Grady, William M. |
Source: | Cancer Epidemiology, Biomarkers & Prevention; Dec2015, Vol. 24 Issue 12, p1890-1897, 8p |
Abstract: | Background: Barrett's esophagus (BE) is a preneoplastic condition in which normal esophageal squamous epithelium (SQ) is replaced by specialized intestinal metaplasia. It is the presumed precursor for esophageal adenocarcinoma (EAC) as well as the strongest risk factor for this cancer. Unfortunately, many patients with BE go undiagnosed under the current BE screening guidelines. The development of noninvasive and accurate BE detection assays could potentially identify many of these undiagnosed BE patients. Methods: DNA methylation is a common epigenetic alteration in BE. Therefore, we conducted a genome-wide methylation screen to identify potential BE biomarkers. Samples from SQ (N = 12), stomach (N = 28), and BE (N = 29) were analyzed and methylation levels at over 485,000 CpG sites were compared. Pyrosequencing assays were used to validate the results and MethyLight assays were developed to detect the methylated alleles in endoscopic brushings. Results: We discovered two genes, B3GAT2 and ZNF793, that are aberrantly methylated in BE. Clinical validation studies confirmed B3GAT2 and ZNF793 methylation levels were significantly higher in BE samples (median = 32.5% and 33.1%, respectively) than in control tissues (median = 2.29% and 2.52%, respectively; P < 0.0001 for both genes). Furthermore, gene-specific MethyLight assays could accurately detect BE (P < 0.0001 for both) in endoscopic brushing samples. Conclusion: B3GAT2 and ZNF793 are hypermethylated in BE, and the methylation status of these genes can be used to detect BE in tissue samples. Impact: These findings support the development of methylated B3GAT2 and ZNF793 as biomarkers for noninvasive assays for the detection of BE. [ABSTRACT FROM AUTHOR] |
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Items | – Name: Title Label: Title Group: Ti Data: Methylated B3GAT2 and ZNF793 Are Potential Detection Biomarkers for Barrett's Esophagus. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Ming+Yu%22">Ming Yu</searchLink><br /><searchLink fieldCode="AR" term="%22O'Leary%2C+Rachele+M%2E%22">O'Leary, Rachele M.</searchLink><br /><searchLink fieldCode="AR" term="%22Kaz%2C+Andrew+M%2E%22">Kaz, Andrew M.</searchLink><br /><searchLink fieldCode="AR" term="%22Morris%2C+Shelli+M%2E%22">Morris, Shelli M.</searchLink><br /><searchLink fieldCode="AR" term="%22Carter%2C+Kelly+T%2E%22">Carter, Kelly T.</searchLink><br /><searchLink fieldCode="AR" term="%22Chak%2C+Amitabh%22">Chak, Amitabh</searchLink><br /><searchLink fieldCode="AR" term="%22Chandar%2C+Apoorva%22">Chandar, Apoorva</searchLink><br /><searchLink fieldCode="AR" term="%22Willis%2C+Joseph+E%2E%22">Willis, Joseph E.</searchLink><br /><searchLink fieldCode="AR" term="%22Moinova%2C+Helen+R%2E%22">Moinova, Helen R.</searchLink><br /><searchLink fieldCode="AR" term="%22Markowitz%2C+Sanford+D%2E%22">Markowitz, Sanford D.</searchLink><br /><searchLink fieldCode="AR" term="%22Brenner%2C+Dean+E%2E%22">Brenner, Dean E.</searchLink><br /><searchLink fieldCode="AR" term="%22Anandabapasathy%2C+Sharmila%22">Anandabapasathy, Sharmila</searchLink><br /><searchLink fieldCode="AR" term="%22Westerhoff%2C+Maria%22">Westerhoff, Maria</searchLink><br /><searchLink fieldCode="AR" term="%22Chao-Jen+Wong%22">Chao-Jen Wong</searchLink><br /><searchLink fieldCode="AR" term="%22Shaheen%2C+Nicholas+J%2E%22">Shaheen, Nicholas J.</searchLink><br /><searchLink fieldCode="AR" term="%22Yanwen+Chen%22">Yanwen Chen</searchLink><br /><searchLink fieldCode="AR" term="%22Barnholtz-Sloan%2C+Jill+S%2E%22">Barnholtz-Sloan, Jill S.</searchLink><br /><searchLink fieldCode="AR" term="%22Grady%2C+William+M%2E%22">Grady, William M.</searchLink> – Name: TitleSource Label: Source Group: Src Data: Cancer Epidemiology, Biomarkers & Prevention; Dec2015, Vol. 24 Issue 12, p1890-1897, 8p – Name: Abstract Label: Abstract Group: Ab Data: Background: Barrett's esophagus (BE) is a preneoplastic condition in which normal esophageal squamous epithelium (SQ) is replaced by specialized intestinal metaplasia. It is the presumed precursor for esophageal adenocarcinoma (EAC) as well as the strongest risk factor for this cancer. Unfortunately, many patients with BE go undiagnosed under the current BE screening guidelines. The development of noninvasive and accurate BE detection assays could potentially identify many of these undiagnosed BE patients. Methods: DNA methylation is a common epigenetic alteration in BE. Therefore, we conducted a genome-wide methylation screen to identify potential BE biomarkers. Samples from SQ (N = 12), stomach (N = 28), and BE (N = 29) were analyzed and methylation levels at over 485,000 CpG sites were compared. Pyrosequencing assays were used to validate the results and MethyLight assays were developed to detect the methylated alleles in endoscopic brushings. Results: We discovered two genes, B3GAT2 and ZNF793, that are aberrantly methylated in BE. Clinical validation studies confirmed B3GAT2 and ZNF793 methylation levels were significantly higher in BE samples (median = 32.5% and 33.1%, respectively) than in control tissues (median = 2.29% and 2.52%, respectively; P < 0.0001 for both genes). Furthermore, gene-specific MethyLight assays could accurately detect BE (P < 0.0001 for both) in endoscopic brushing samples. Conclusion: B3GAT2 and ZNF793 are hypermethylated in BE, and the methylation status of these genes can be used to detect BE in tissue samples. Impact: These findings support the development of methylated B3GAT2 and ZNF793 as biomarkers for noninvasive assays for the detection of BE. [ABSTRACT FROM AUTHOR] – Name: Abstract Label: Group: Ab Data: <i>Copyright of Cancer Epidemiology, Biomarkers & Prevention is the property of American Association for Cancer Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1158/1055-9965.EPI-15-0370 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 8 StartPage: 1890 Titles: – TitleFull: Methylated B3GAT2 and ZNF793 Are Potential Detection Biomarkers for Barrett's Esophagus. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Ming Yu – PersonEntity: Name: NameFull: O'Leary, Rachele M. – PersonEntity: Name: NameFull: Kaz, Andrew M. – PersonEntity: Name: NameFull: Morris, Shelli M. – PersonEntity: Name: NameFull: Carter, Kelly T. – PersonEntity: Name: NameFull: Chak, Amitabh – PersonEntity: Name: NameFull: Chandar, Apoorva – PersonEntity: Name: NameFull: Willis, Joseph E. – PersonEntity: Name: NameFull: Moinova, Helen R. – PersonEntity: Name: NameFull: Markowitz, Sanford D. – PersonEntity: Name: NameFull: Brenner, Dean E. – PersonEntity: Name: NameFull: Anandabapasathy, Sharmila – PersonEntity: Name: NameFull: Westerhoff, Maria – PersonEntity: Name: NameFull: Chao-Jen Wong – PersonEntity: Name: NameFull: Shaheen, Nicholas J. – PersonEntity: Name: NameFull: Yanwen Chen – PersonEntity: Name: NameFull: Barnholtz-Sloan, Jill S. – PersonEntity: Name: NameFull: Grady, William M. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 12 Text: Dec2015 Type: published Y: 2015 Identifiers: – Type: issn-print Value: 10559965 Numbering: – Type: volume Value: 24 – Type: issue Value: 12 Titles: – TitleFull: Cancer Epidemiology, Biomarkers & Prevention Type: main |
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