Simultaneous methylation of the E-cadherin and p16 gene promoter in breast cancer.

V H Deshmane MDa, I S Fentiman MDb, I R Hart PhDc

aDepartment of Surgical Oncolgy Hinduja Hospital, Mumbai,India. bBreast Unit, Guy's Hospital, London, UK. cRichard Dimbleby Department of Cancer Research/ICRF Lab, St Thomas' Hospital, London, UK.

Methylation of the promoter region of a gene provides a mechanism by which gene expression may be down regulated. The E-cadherin gene mediates homotypic cell-cell adhesion, and loss of adhesion is considered a critical event in the development of metastasis. The p16 gene is a cyclin dependent kinase inhibitor, controlling orderly development of the proliferating cell. It controls progress from G1 to S phase and inactivation of p16 is a common event in human neoplasia. Thus, when considered together, the methylation status of these genes provides an indication of the proliferative state of the tumour as well as its potential to invade and metastasize. Aim: To assess the methylation status of the E-cadherin and p16 gene promoter in breast tumours Methods: Using Methylation-specific PCR (MSP) the methylation status of the E-cadherin and p16 gene promoter was established in a cohort of 64 patients with breast cancer. Results: The overall incidence of methylation involving either the E-cadherin gene (84%) or the p16 gene (79%) was as high as 95%. In 43 patients (67%), both gene promoters were simultaneously methylated while both promoters were unmethylated in 3 patients (5%). Conclusions: Promoter methylation occurs frequently in breast cancer and multiple genes may be simultaneously affected. Assessment of multiple genes within a tumour may provide a "methylation profile" of that tumour. Such profiling could prove useful in identifying a more aggressive subset of cells within a tumour and provide vital information for the individualization of treatment in patients with breast cancer.

KEY WORDS: methylation, E-cadherin, p16, breast cancer, profile.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Molecular Pathology.