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How DNA is packaged in the cell: changes in cancer of the womb

If it were laid out in a straight line, the DNA contained in each cell of the body would stretch for about 2 metres.  In order to package DNA neatly within a cell, it is wrapped up tightly by packaging proteins into a structure called chromatin. As well as being the means by which large amounts of DNA are packed into a small space, packaging DNA into chromatin also helps control gene activity, and in some cases this seems to go wrong in cancer.

In cancerous cells the chromatin can be changed in such a way that cells are stuck in an immature state, and this is believed to help tumour growth. Polycomb proteins are a group of proteins that regulate chromatin structure, and increasing knowledge indicates that they play a part in some of the changes that cause cancer. One of the clearest examples of a link between these Polycomb protein complexes and cancer development can be seen in endometrial stromal sarcoma (ESS). ESS is a rare form of cancer of the womb or uterus. This tumour develops in the endometrium, which is the layer of tissue that lines the inside of the womb. ESS can develop when a group of cells, called stromal cells, grow and divide into another type of cell, called decidual cells. The stromal cells develop into decidual cells during each menstrual cycle, as part of preparing the womb for a possible pregnancy. During ESS, a specific polycomb protein is mutated, which encourages cells to grow and divide, and also stops a natural control mechanism which causes damaged or unwanted cells to die.

Dr Jenner and his team have found that the mutated polycomb protein in ESS is unable to function properly, and they will be using their Worldwide Cancer Research grant to look at the changes this causes to chromatin and how this may cause tumours to develop. It is hoped that this will also give us a broader understanding of the role of polycomb proteins in other types of cancer.