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New evidence: cancer is a stem cell disease

Publication date: Jan 12, 2007 11:55:34 AM

Evidence that stem cells are the cells of origin for cancer is published online today (31st December 2006) in Nature Genetics.

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 (e.g. 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 (University College London). 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 (University College London Hospital NHS Foundation) and The Eve Appeal charity .

Dr Martin Widschwendter, of UCL’s IfWH, says: “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.

The Eve Appeal is fundraising for the next stage of Dr Widschwendter’s work. Donations can be made online at www.eveappeal.org.uk; or by contacting the charity on 0207 380 6900 or office@eveappeal.org.uk .

-Ends-

Notes for Editors

1. For more information, please contact:

Professor Ian Jacobs, MBBS, MD FRCOG, on +44 (0)207 380 9747, mobile 07734 592233, e-mail: ian.jacobs@ucl.ac.uk

Dr Martin Widschwendter, UCL Department of Gynaecological Oncology, mobile + 44 (0)7908 767340 e- mail m.widschwendter@ucl.ac.uk

Jane Lyons, The Eve Appeal, Tel: +44 (0) 207 380 6900, Mobile: +44 (0)7831 683307, Email: comms@eveappeal.org.uk

Ruth Metcalfe, UCL Media Relations, Tel: +44 (0) 20 7679 9739, Mobile: +44 (0)7990 675 947, out of hours: +44 (0)7917 271 364, Email: r.metcalfe@ucl.ac.uk

2. The paper 'Epigenetic stem cell signature in cancer' will be published on the Nature Genetics's website on 31December at 1800 London time / 1300 US Eastern time. See http://dx.doi.org/10.1038/ng1941

About The Eve Appeal charity

The Eve Appeal charity fundraises for research into gynaecological cancers with a current focus on ovarian cancer. There are currently 7,000 cases of ovarian cancer in the UK every year and 5,000 deaths, making ovarian cancer the fourth biggest cancer killer of women. About 10 per cent of ovarian cancer cases come from high risk families. High risk families are where more than one woman has had ovarian cancer or there is one woman with ovarian cancer and others in the same family with breast cancer diagnosed at an early age.

To find out more about the IfWH visit the website: www.ucl.ac.uk/instituteforwomenshealth

About UCL

Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. In the government’s most recent Research Assessment Exercise, 59 UCL departments achieved top ratings of 5* and 5, indicating research quality of international excellence.

UCL is the fourth-ranked UK university in the 2006 league table of the top 500 world universities produced by the Shanghai Jiao Tong University. UCL alumni include Mahatma Gandhi (Laws 1889, Indian political and spiritual leader); Jonathan Dimbleby (Philosophy 1969, writer and television presenter); Junichiro Koizumi (Economics 1969, Prime Minister of Japan); Lord Woolf (Laws 1954, Lord Chief Justice of England & Wales); Alexander Graham Bell (Phonetics 1860s, inventor of the telephone), and members of the band Coldplay.

Background information

Stem cells are primal cells common to all multicellular organisms that retain the ability to renew themselves through cell division and can differentiate into a wide range of specialized cell types. The two categories of human stem cells are embryonic stem cells, derived from blastocysts, and adult stem cells, derived from umbilical cord blood or bone marrow. In a blastocyst of a developing embryo, stem cells differentiate into all of the specialised embryonic tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing specialized cells. As stem cells can be readily grown and transformed into specialized tissues such as muscles or nerves through cell culture, their use in medical therapies has been proposed.

A gene is the unit of heredity in every living organism. Genes are encoded in an organism's genome, composed of DNA, and direct the physical development and behaviour of the organism. Most genes encode proteins, which are biological macromolecules comprising linear chains of amino acids that affect most of the chemical reactions carried out by the cell. Molecules that result from gene expression, whether RNA or protein, are collectively known as gene products. Most genes contain non-coding regions, that do not code for the gene products, but often regulate gene expression. A critical non-coding region is the promoter, a short DNA sequence that is required for initiation of gene expression.

Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the biological development of a cell. All known cells have DNA. DNA is a long polymer of nucleotides (a polynucleotide) that encodes the sequence of amino acid residues in proteins, using the genetic code.

DNA methylation is a type of chemical modification of DNA. Mainly, DNA methylation involves the addition of a methyl group to cytosine, which is one of the four bases, DNA consists of. DNA methylation in the promoter region leads to irrevocable silencing of a gene.

Epigenetics is the study of epigenetic inheritance, a set of reversible or irreversible heritable changes in gene function or other cell phenotype that occur without a change in DNA sequence. DNA methylation is the best known epigenetic alteration.

White blood cells or leucocytes are cells which form a component of the blood. They are produced in the bone marrow and help to defend the body against infectious disease and foreign materials as part of the immune system.