Promoter hypermethylation of CDH13 is a common, early event in human esophageal adenocarcinogenesis and correlates with clinical risk factors
dc.contributor.author | Jin, Zhe | en_US |
dc.contributor.author | Cheng, Yulan | en_US |
dc.contributor.author | Olaru, Alexandru | en_US |
dc.contributor.author | Kan, Takatsugu | en_US |
dc.contributor.author | Yang, Jian | en_US |
dc.contributor.author | Paun, Bogdan | en_US |
dc.contributor.author | Ito, Tetsuo | en_US |
dc.contributor.author | Hamilton, James P. | en_US |
dc.contributor.author | David, Stefan | en_US |
dc.contributor.author | Agarwal, Rachana | en_US |
dc.contributor.author | Selaru, Florin M. | en_US |
dc.contributor.author | Sato, Fumiaki | en_US |
dc.contributor.author | Abraham, John M. | en_US |
dc.contributor.author | Beer, David G. | en_US |
dc.contributor.author | Mori, Yuriko | en_US |
dc.contributor.author | Shimada, Yutaka | en_US |
dc.contributor.author | Meltzer, Stephen J. | en_US |
dc.date.accessioned | 2008-10-01T15:23:20Z | |
dc.date.available | 2009-12-01T16:53:14Z | en_US |
dc.date.issued | 2008-11-15 | en_US |
dc.identifier.citation | Jin, Zhe; Cheng, Yulan; Olaru, Alexandru; Kan, Takatsugu; Yang, Jian; Paun, Bogdan; Ito, Tetsuo; Hamilton, James P.; David, Stefan; Agarwal, Rachana; Selaru, Florin M.; Sato, Fumiaki; Abraham, John M.; Beer, David G.; Mori, Yuriko; Shimada, Yutaka; Meltzer, Stephen J. (2008). "Promoter hypermethylation of CDH13 is a common, early event in human esophageal adenocarcinogenesis and correlates with clinical risk factors." International Journal of Cancer 123(10): 2331-2336. <http://hdl.handle.net/2027.42/60976> | en_US |
dc.identifier.issn | 0020-7136 | en_US |
dc.identifier.issn | 1097-0215 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/60976 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=18729198&dopt=citation | en_US |
dc.description.abstract | Although the CDH13 gene has been shown to undergo epigenetic silencing by promoter methylation in many types of tumors, hypermethylation of this gene in Barrett's-associated esophageal adenocarcinogenesis has not been studied. Two hundred fifty-nine human esophageal tissues were therefore examined for CDH13 promoter hypermethylation by real-time methylation-specific PCR. CDH13 hypermethylation showed discriminative receiver-operator characteristic curve profiles, sharply demarcating esophageal adenocarcinoma (EAC) from esophageal squamous cell carcinoma (ESCC) and normal esophagus (NE) ( p < 0.0001). CDH13 normalized methylation values (NMV) were significantly higher in Barrett's esophagus (BE), dysplastic BE (D) and EAC than in NE ( p < 0.0000001). CDH13 hypermethylation frequency was 0% in NE but increased early during neoplastic progression, rising to 70% in BE, 77.5% in D and 76.1% in EAC. Both CDH13 hypermethylation frequency and its mean NMV were significantly higher in BE with than without accompanying EAC. In contrast, only 5 (19.2%) of 26 ESCCs exhibited CDH13 hypermethylation. Furthermore, both CDH13 hypermethylation frequency and its mean NMV were significantly higher in EAC than in ESCC, as well as in BE or D vs . ESCC. Interestingly, mean CDH13 NMV was significantly lower in short-segment than in long-segment BE, a known clinical risk factor for neoplastic progression. Similarly, BE segment length was significantly lower in specimens with unmethylated than with methylated CDH13 promoters. 5-aza-2′-deoxycytidine treatment of OE33 EAC and KYSE220 ESCC cells reduced CDH13 methylation and increased CDH13 mRNA expression. These findings suggest that hypermethylation of CDH13 is a common, tissue-specific event in human EAC, occurs early during BE-associated neoplastic progression, and correlates with known clinical neoplastic progression risk factors. © 2008 Wiley-Liss, Inc. | en_US |
dc.format.extent | 215015 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Cancer Research, Oncology and Pathology | en_US |
dc.title | Promoter hypermethylation of CDH13 is a common, early event in human esophageal adenocarcinogenesis and correlates with clinical risk factors | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Oncology and Hematology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Division of General Thoracic Surgery, Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD | en_US |
dc.contributor.affiliationother | Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD ; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD ; Fax: +410-502-1329. ; Division of Gastroenterology, Department of Medicine, Johns Hopkins University School of Medicine, 1503 E, Jefferson Street, Rm. 112, Baltimore, MD 21231, USA | en_US |
dc.identifier.pmid | 18729198 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/60976/1/23804_ftp.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1002/ijc.23804 | en_US |
dc.identifier.source | International Journal of Cancer | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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