New evidence: cancer is a stem cell disease

A key step in the normal development of stem cells is the suppression of genes which when later switched on lead to the differentiation of cells into specific mature cell types (eg breast, ovarian or bowel cells). In normal stem cells, the suppression of these genes is reversible. However in cancer cells these critical genes are modified by a process called DNA methylation, which predisposes to cancer by causing permanent and irreversible gene suppression.

Lead author of the research Dr Martin Widschwendter and his team are based at the Institute for Women's Health (IfWH), directed by Professor Ian Jacobs at UCL. Additional work in the field of colorectal cancer was also carried out by Dr Laird's group at the Norris Comprehensive Cancer Centre at the University of Southern California in Los Angeles.

The work involved analysis of 200 different genes in adult stem cells and normal and cancerous tissues of breast, ovary, bowel and lung and was funded by UCL, UCLH  and The Eve Appeal charity.

Dr Martin Widschwendter, of UCL's IfWH, said: "This research has proven for the first time that acquisition of promoter DNA methylation can keep stem cells at an 'undifferentiated' early stage of development which predisposes them to cancer. We have also identified this abnormal DNA methylation in the bone marrow stem cells of women with cancer. These findings open a complete new window of opportunity to identify women at risk of breast or ovarian cancer independently of their family history. 90 per cent of ovarian and breast cancers in the UK occur in women who do not come from a high risk family.

"In addition, identification of factors which contribute to the abnormal DNA methylation process in stem cells may provide us with new strategies to prevent these deadly diseases. We have this next stage of the research lined up and ready to go and just need more funding to press ahead.  It is possible that in two years' time we could be introducing a whole new way of predicting cancer risk - based on a simple blood test."

Professor Ian Jacobs, Director of UCL's IfWH, Medical Director of The Eve Appeal and Vice-Dean for Research at UCL, says: "Martin Widschwendter is an outstanding doctor and scientist. His work is of great importance and is likely to have a major impact on our ability to identify women most at risk of ovarian or breast cancer. It may enable us to introduce a much more targeted way of early detection and cancer prevention in women. The hope is that it will enable us to focus resources used for screening and prevention on the group of women with these abnormalities rather than the entire population."

The next stage of the research will involve identifying DNA methylation patterns in white blood cells to predict breast and ovarian cancer, and identifying how cancer predisposing conditions contribute to alterations in DNA methylation patterns in the circulation and white blood cells DNA.