Methylation pattern of CDH13 gene in digestive tract cancers

Hibi, Kenji; Kodera, Yasuhiro; Ito, Katsuki; Akiyama, Seiji; Nakao, Akimasa

doi:10.1038/sj.bjc.6602095

Cited by 40 publications

(25 citation statements)

References 12 publications

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“…In the present study, we observed that CDH13 and PGP9.5 are also methylated in gastric mucosae with H. pylori infection, which is consistent with an earlier study showing CDH13 to be aberrantly methylated in gastric cancer (32). CDH13 (also known as H-cadherin) encodes a protein related to the cadherin superfamily of cell adhesion molecules and is involved in suppressing cell growth, invasion, and metastasis (33,34).…”

Section: Discussionsupporting

confidence: 92%

LINE-1 Hypomethylation Is Associated with Increased CpG Island Methylation in Helicobacter pylori–Related Enlarged-Fold Gastritis

Yamamoto¹,

Toyota²,

Suzuki³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: The molecular mechanism by which Helicobacter pylori infection leads to gastric cancer is not fully understood. Similarly, patients with enlargedfold (EF+) gastritis, one cause of which is H. pylori infection, have an increased risk for gastric cancer, although again molecular mechanism is unclear. In the present study, we analyzed the methylation status of long interspersed nucleotide elements (LINE-1) and three cancer-related genes in a panel of gastric mucosae, with or without EF+ gastritis. Methods: We used bisulfite pyrosequencing to assess the levels of LINE-1, CDH1, CDH13, and PGP9.5 methylation in 78 gastric mucosa specimens from 48 patients.

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Section: Discussionsupporting

confidence: 92%

LINE-1 Hypomethylation Is Associated with Increased CpG Island Methylation in Helicobacter pylori–Related Enlarged-Fold Gastritis

Yamamoto¹,

Toyota²,

Suzuki³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Highly invasive growth pattern (Berx et al 1998) Up-regulated expression Epithelial ovarian cancer (Sato et al 1998;Maruyama et al 2001;Toyooka et al 2001;Toyooka et al 2002;Roman-Gomez et al 2003;Hibi et al 2004;Sakai et al 2004;Kim et al 2005;Wang et al 2007;Brock et al 2008;Jin et al 2008;Yan et al 2008) LOH and promoter methylation Ovary Skin (BCC and SCC) Diffuse large B cell lymphoma HCC Tumor invasion; increased cell proliferation and resistance to apoptosis (Kawakami et al 1999;Takeuchi et al 2002a;Takeuchi et al 2002b;Ogama et al 2004;Chan et al 2008) Expression in intratumoral endothelium…”

Section: Somatic Mutations Breast (Ilc) Gastric (Dgc) Pancreasmentioning

confidence: 99%

Involvement of Members of the Cadherin Superfamily in Cancer

Berx¹,

Roy²

2009

Cold Spring Harbor Perspectives in Biology

564

489

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We review the role of cadherins and cadherin-related proteins in human cancer. Cellular and animal models for human cancer are also dealt with whenever appropriate. E-cadherin is the prototype of the large cadherin superfamily and is renowned for its potent malignancy suppressing activity. Different mechanisms for inactivating E-cadherin/CDH1 have been identified in human cancers: inherited and somatic mutations, aberrant protein processing, increased promoter methylation, and induction of transcriptional repressors such as Snail and ZEB family members. The latter induce epithelial mesenchymal transition, which is also associated with induction of "mesenchymal" cadherins, a hallmark of tumor progression. VE-cadherin/CDH5 plays a role in tumor-associated angiogenesis. The atypical T-cadherin/ CDH13 is often silenced in cancer cells but up-regulated in tumor vasculature. The review also covers the status of protocadherins and several other cadherin-related molecules in human cancer. Perspectives for emerging cadherin-related anticancer therapies are given.

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“…[16][17][18] Furthermore, there is a growing body of evidence showing that abnormal methylation of DNA can be an early event in carcinogenesis and can serve as an early cancer detection biomarker, 15 including in EAC. [17][18][19][20] Hypermethylation of CDH13 has been described in many human cancers, 8,14,[21][22][23][24][25][26][27][28][29] including ESCC 24,29 ; however, hypermethylation of CDH13 in precancerous lesions such as Barrett's metaplasia (BE), as well as in BE-associated EAC, is an area that still remains to be explored. We investigated hypermethylation of the CDH13 promoter by real-time quantitative methylation-specific PCR (qMSP) in 259 endoscopic esophageal biopsy specimens of differing histologies and correlated these data with clinicopathological features.…”

Section: Cdh13mentioning

confidence: 99%

Promoter hypermethylation of CDH13 is a common, early event in human esophageal adenocarcinogenesis and correlates with clinical risk factors

Jin

Cheng

Olaru

et al. 2008

Intl Journal of Cancer

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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 receiveroperator 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 0 -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.Key words: CDH13; hypermethylation; EAC; ESCC CDH13 (also known as H-cadherin and T-cadherin), a member of the cadherin gene superfamily, was isolated and has been mapped to 16q24, 1 a locus that frequently undergoes deletion in human cancers, including esophageal carcinoma. 2,3 In contrast to other known cadherins such as E-cadherin, N-cadherin and P-cadherin, which are transmembrane proteins, CDH13 lacks conventional transmembrane and cytoplasmic domains and is attached to the plasma membrane through a glycosyl phosphatidyl inositol anchor.1,4-6 Several studies have suggested that CDH13 functions as a tumor suppressor gene and possesses potent antitumor activity in several human cancers both in vitro and in vivo.7-10 Overexpression of CDH13 in human breast carcinoma cells (MDAMB435) reduced their invasive potential in vitro and tumor formation in vivo, accompanied by reversion from invasive to normal cell morphology.7 Loss of CDH13 protein expression is associated with tumorigenicity of human non-small cell lung cancer cells. 8,9 In cutaneous squamous cell carcinoma cells, overexpression of CDH13 induced a delay in the G 2 /M phase of...

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Methylation pattern of CDH13 gene in digestive tract cancers

Cited by 40 publications

References 12 publications

LINE-1 Hypomethylation Is Associated with Increased CpG Island Methylation in Helicobacter pylori–Related Enlarged-Fold Gastritis

LINE-1 Hypomethylation Is Associated with Increased CpG Island Methylation in Helicobacter pylori–Related Enlarged-Fold Gastritis

Involvement of Members of the Cadherin Superfamily in Cancer

Promoter hypermethylation of CDH13 is a common, early event in human esophageal adenocarcinogenesis and correlates with clinical risk factors

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