Back to Search
Start Over
Frequent Aberrant Methylation of the CDH4 Gene Promoter in Human Colorectal and Gastric Cancer
- Source :
- Cancer Research. 64:8156-8159
- Publication Year :
- 2004
- Publisher :
- American Association for Cancer Research (AACR), 2004.
-
Abstract
- Gene promoter methylation causes loss of tumor suppressor genes function in human cancer. Here, we show that the CDH4 gene, a member of the cadherin family encoding for R-cadherin, contains a CpG island located at the 5′ of the first exon, which functions as a promoter element and is frequently affected by methylation in human cancer. By using methylation-specific PCR and reverse transcription-PCR in human cancer cell lines, promoter methylation could be directly linked to loss of gene expression. After treatment with the demethylating agent 5-aza-2-deoxycytidine, expression could be restored. Analysis of human primary tumors revealed that the CDH4 gene is methylated in 78% (38 of 49) of colorectal and 95% (20 of 21) of gastric carcinomas. CDH4 methylation was not detected in nonneoplastic colonic (0 of 10) and stomach (0 of 10) tissues or in peripheral blood (0 of 17). CDH4 methylation was detected in histologically normal tissues located in proximity of the neoplasms, indicating that CDH4 methylation is an early event in gastrointestinal tumor progression. We also proved that CDH4 methylation can be revealed in the peripheral blood of cancer patients. Our results indicate that CDH4 may act as a tumor suppressor gene in human gastrointestinal tumors and can potentially be used as an early diagnostic marker for gastrointestinal tumorigenesis.
- Subjects :
- Cancer Research
Pathology
medicine.medical_specialty
Tumor suppressor gene
Biology
medicine.disease_cause
chemistry.chemical_compound
Stomach Neoplasms
medicine
Humans
Promoter Regions, Genetic
Stomach cancer
DNA Primers
Base Sequence
Reverse Transcriptase Polymerase Chain Reaction
Cancer
Promoter
Methylation
DNA Methylation
medicine.disease
Demethylating agent
Oncology
chemistry
DNA methylation
Cancer research
Colorectal Neoplasms
Carcinogenesis
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 64
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....bac01cb5d9f69bdaa81aac140d47a294