USC/Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, 1441 Eastlake Avenue, MS 8302L, Los Angeles, California, CA 90089-9181, USA

Correspondence to: M Widschwendter, E-mail: Martin.Widschwendter@uibk.ac.at

Knowledge about breast carcinogenesis has accumulated during the last decades but has barely been translated into strategies for early detection or prevention of this common disease. Changes in DNA methylation have been recognized as one of the most common molecular alterations in human neoplasia and hypermethylation of gene-promoter regions is being revealed as one of the most frequent mechanisms of loss of gene function. The heritability of methylation states and the secondary nature of the decision to attract or exclude methylation support the idea that DNA methylation is adapted for a specific cellular memory. According to Hanahan and Weinberg, there are six novel capabilities a cell has to acquire to become a cancer cell: limitless replicative potential, self-sufficiency in growth signals, insensitivity to growth-inhibitory signals, evasion of programmed cell death, sustained angiogenesis and tissue invasion and metastasis. This review highlights how DNA-methylation contributes to these features and offers suggestions about how these changes could be prevented, reverted or used as a 'tag' for early detection of breast cancer or, preferably, for detection of premalignant changes.

Oncogene (2002) 21, 5462-5482. doi:10.1038/sj.onc.1205606

breast cancer; DNA methylation; carcinogenesis; prevention; early detection