Promoter hypermethylation of CDH13 is a common, early event in human esophageal adenocarcinogenesis and correlates with clinical risk factors
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.
2008-11-15
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>
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.Publisher
Wiley Subscription Services, Inc., A Wiley Company
ISSN
0020-7136 1097-0215
Other DOIs
PMID
18729198
Types
Article
URI
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=18729198&dopt=citationMetadata
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