BRCA1 methylation: a significant role in tumour development?
Cancer is a multistep process resulting from an accumulation of genetic mutations leading to dysfunction of critical genes, including tumour suppressor genes. Epigenetic changes are now also recognised as an important alternative mechanism of gene inactivation. In particular, aberrant methylation of the promoter region of a gene can lead to silencing ultimately contributing to the initiation or malignant progression of tumours. BRCA1, a breast and ovarian cancer susceptibility gene, is a tumour suppressor gene involved in the maintenance of genome integrity. Recent evidence for BRCA1 hypermethylation corroborates the view that this epigenetic alteration may play a determinant role in tumour suppressor silencing and possibly tumorigenesis. Here, we offer a summary of the data providing evidence for BRCA1 hypermethylation in tumours, and an investigation into the associated mechanism leading to BRCA1 silencing. We also discuss the impact of BRCA1 hypermethylation, as a form of epigenetic change, versus BRCA1 genetic mutations in tumour development.
Division of Medical and Molecular Genetics, GKT School of Medicine, 8th Floor Guy's Tower, Guy's Hospital, London SE1 9RT, UK. catteau@cancer.org.uk
Aurélie
A
Catteau
Joanna R
JR
Morris
D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D019398:Genes, BRCA1; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D010051:Ovarian Neoplasms / Q000209:etiology / Q000235:genetics*; D011401:Promoter Regions, Genetic