Epigenetic alterations of CDH1 and APC genes: Relationship with activation of Wnt/β-catenin Pathway in invasive ductal carcinoma of breast

Prasad, Chandra Prakash; Mirza, Sameer; Sharma, Gayatri; Prashad, Rajinder; Dattagupta, S; Rath, Goutam; Ralhan, Ranju

doi:10.1016/j.lfs.2008.06.019

Cited by 89 publications

(75 citation statements)

References 50 publications

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“…In these cases, methylation specific PCR fragment might be the result of contamination with infiltrating leukocytes, making the detection and interpretation of tumor-associated distorted methylation patterns more complicated (Lombaerts et al, 2004). Overall, our data corroborate the findings reported by earlier studies that CDH1 promoter hypermethylation is responsible for its heterogeneous downregulation in ductal cell carcinoma (Graff et al, 2000;Caldeira et al, 2006;Prasad et al, 2008).…”

Section: Discussionsupporting

confidence: 90%

“…The frequency of CDH1 promoter methylation in breast cancer patients in our study was 57.8% as against 14.8% of the corresponding normal breast samples. The frequency of CDH1 methylation in our study is similar to other studies conducted on breast cancer patients (Shinozaki et al, 2005;Prasad et al, 2008). Other previous studies have shown varying frequencies of CDH1 methylation viz; 72% (Caldeira et al, 2006), 26.1% (Hu et al, 2002) , 21.7% (Sebova et al, 2011), 94% (Shargh et al, 2011) in breast cancer tissues from different population.…”

Section: Discussionsupporting

confidence: 90%

“…Reduced expression of E-cadherin is regarded as one of the main molecular events involved in the dysfunction of the cell-cell adhesion system, triggering cancer invasion and metastasis (Debies and Welch, 2001). Hypermethylation in CDH1 gene and its reduced expression in gut, lung, prostate and breast cancers, which could be due to the disruption of intercellular adhesion and impairment of β-catenin mediated transactivation of cadherin-catenin complex (Graff et al, 1995;Sadot et al, 1998;Tamura et al, 2000;Hu et al, 2002;Caldeira et al, 2006;Prasad et al, 2008;Zheng et al, 2012) has been reported.…”

Section: Discussionmentioning

confidence: 99%

“…Loss of E-cadherin expression was reported in 85% of invasive lobular carcinomas (ILCs) and lobular carcinoma in situ (LCIS) (Sarrio et al, 2004;Yoder et al, 2007). However, ductal histology often presents with varying levels of expression associated with epigenetic transcriptional downregulation (Graff et al, 1995;Nass et al, 2000;Prasad et al, 2008). Analysis of CDH1 methylation in breast cancers and other tumor types has shown that aberrant hypermethylation of CpG islands in CDH1 promoter region often occurs prior to invasion, indicating it to be an early event in tumorigenesis (Graff et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Loss of Expression and Aberrant Methylation of the CDH1 (E-cadherin) Gene in Breast Cancer Patients from Kashmir

Asiaf

Ahmad²,

Aziz³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Aberrant promoter hypermethylation has been recognized in human breast carcinogenesis as a frequent molecular alteration associated with the loss of expression of a number of key regulatory genes and may serve as a biomarker. The E-cadherin gene (CDH1), mapping at chromosome 16q22, is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. The aim of our study was to assess the methylation pattern of CDH1 and to correlate it with the expression of E-cadherin, clinicopathological parameters and hormone receptor status in breast cancer patients of Kashmir. Materials and Methods: Methylation specific PCR (MSP) was used to determine the methylation status of CDH1 in 128 invasive ductal carcinomas (IDCs) paired with the corresponding normal tissue samples. Immunohistochemistry was used to study the expression of E-cadherin, ER and PR. Results: CDH1 hypermethylation was detected in 57.8% of cases and 14.8% of normal adjacent controls. Reduced levels of E-cadherin protein were observed in 71.9% of our samples. Loss of E-cadherin expression was significantly associated with the CDH1 promoter region methylation (p<0.05, OR=3.48, CI: 1.55-7.79). Hypermethylation of CDH1 was significantly associated with age at diagnosis (p=0.030), tumor size (p=0.008), tumor grade (p= 0.024) and rate of node positivity or metastasis (p=0.043). Conclusions: Our preliminary findings suggest that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression. We found significant differences in tumor-related CDH1 gene methylation patterns relevant to tumor grade, tumor size, nodal involvement and age at diagnosis of breast tumors, which could be extended in future to provide diagnostic and prognostic information.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Loss of Expression and Aberrant Methylation of the CDH1 (E-cadherin) Gene in Breast Cancer Patients from Kashmir

Asiaf

Ahmad²,

Aziz³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…A DNA methylation mechanism was involved in the modification of these signaling pathways. Hypermethylation in the promoters of the Wnt pathway associated with adenomatous polyposis coli and E-cadherin was recently reported (22)(23)(24). Based on our data, a number of other members involved in the Wnt pathway also displayed alterations in the methylation status in associated CpG islands.…”

Section: Discussionmentioning

confidence: 97%

Array-based profiling of the differential methylation status of CpG islands in hepatocellular carcinoma cell lines

Liu

Zheng²,

Liu³

et al. 2010

Oncology Letters

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Abstract. Alterations in the DNA methylation status particularly in CpG islands are involved in the initiation and progression of many types of human cancer. A number of DNA methylation alterations have been reported in hepatocellular carcinoma (HCC). However, a systematic analysis is required to elucidate the relationship between differential DNA methylation status and the characteristics and progression of HCC. In the present study, a global analysis of DNA methylation using a human CpG-island 12K array was performed on a number of HCC cell lines of different origin and metastatic potential. Based on a standard methylation alteration ratio of ≥2 or ≤0.5, 58 CpG island sites and 66 tumor-related genes upstream, downstream or within were identified. This study showed a series of CpG island methylation alterations in the HCC cell lines. The expression of various oncogenes, tumor suppressor genes and other key genes were up-or downregulated, respectively, resulting in CpG island hypomethylation or hypermethylation accordingly. To conclude, a foundation has been provided for screening CpG island methylation profiles as HCC biological markers.

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Epigenetic Alterations as Contributors to the Pathogenesis, Detection, Prognosis and Treatment of Human Pre-invasive Neoplasia

David¹,

Meltzer²

2010

Pre-Invasive Disease: Pathogenesis and Clinical Management

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Epigenetic alterations of CDH1 and APC genes: Relationship with activation of Wnt/β-catenin Pathway in invasive ductal carcinoma of breast

Cited by 89 publications

References 50 publications

Loss of Expression and Aberrant Methylation of the CDH1 (E-cadherin) Gene in Breast Cancer Patients from Kashmir

Loss of Expression and Aberrant Methylation of the CDH1 (E-cadherin) Gene in Breast Cancer Patients from Kashmir

Array-based profiling of the differential methylation status of CpG islands in hepatocellular carcinoma cell lines

Epigenetic Alterations as Contributors to the Pathogenesis, Detection, Prognosis and Treatment of Human Pre-invasive Neoplasia

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