Hypermethylation of the promoter region of the E-cadherin gene (CDH1) in sporadic and ulcerative colitis associated colorectal cancer
Authors:
- J M WheelerJWJ M Wheeler
- H C KimHKH C Kim
- J A EfstathiouJEJ A Efstathiou
- M IlyasMIM Ilyas
- N J MortensenNMN J Mortensen
- W F BodmerW F Bodmer
Open Access
Abstract
BACKGROUND: Ulcerative colitis associated colorectal cancer (UCACRC) has several distinctive clinicopathological and genetic features which differ from sporadic colorectal cancer (SCRC). Hypermethylation of the E-cadherin gene (CDH1) has not been described previously in colorectal cancer. AIMS: A panel of SCRC and UCACRC were investigated for mutations inCDH1, and for hypermethylation of the promoter region of CDH1. SUBJECTS AND METHODS: DNA was available from 14 patients with UCACRC and from 14 with SCRC. All exons ofCDH1 were amplified with the polymerase chain reaction (PCR) and screened using single strand conformational polymorphism and direct sequencing. Hypermethylation of theCDH1 promoter region was determined by methylation specific PCR following bisulphite modification, and compared with E-cadherin protein expression from a previous immunohistochemistry study. RESULTS: Thirteen of 28 cancers (46%) were hypermethylated in theCDH1 promoter region—eight cancers (57%) in the UCACRC group and five cancers (36%) in the SCRC group (NS)—and this correlated with reduced E-cadherin expression (pCDH1 in either group although there were several polymorphisms. CONCLUSION: We have demonstrated hypermethylation of the promoter region inCDH1 in 46% of colorectal cancers studied. There was no difference between the UCACRC and SCRC groups. Just as there are specific differences in the genetic changes between UCACRC and SCRC, there is also likely to be a large degree of overlap among the genetic pathways of these cancers.Keywords
This publication has 34 references indexed in Scilit:
- Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines.1997
- INFLAMMATORY BOWEL DISEASE AND CANCERGastroenterology Clinics of North America, 1997
- BAT-26, an indicator of the replication error phenotype in colorectal cancers and cell lines.1997
- Bcl-2 expression in colorectal tumors: evidence of different pathways in sporadic and ulcerative-colitis-associated carcinomas.1996
- Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands.Proceedings of the National Academy of Sciences, 1996
- Cell Adhesion: The Molecular Basis of Tissue Architecture and MorphogenesisCell, 1996
- E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas.1995
- Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas.Proceedings of the National Academy of Sciences, 1995
- 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancersNature Medicine, 1995
- Adenomatous polyposis coli gene mutations in ulcerative colitis-associated dysplasias and cancers versus sporadic colon neoplasms.1995