Researchers have discovered that many cells in the lining of the human uterus have cancer-driving mutations in their DNA from an early point in life, even though these cells appear normal under the microscope.
New research published in Nature, reveals that a high number of apparently healthy uterine cells carry driver mutations. The researchers think that many of these mutations have arisen early in life, often already during childhood, despite the fact that uterine cancer predominantly affects older women.
'New technologies and approaches to investigating DNA mutations in normal tissues are providing profound insights into the procession of genetic changes that convert a normal cell into a cancer cell. The results indicate that, although most cancers occur at relatively advanced ages, the genetic changes that underlie them may have started early in life and we may have been incubating the developing cancer for most of our lifetime' said corresponding author Professor Sir Mike Stratton, Director of the Wellcome Sanger Institute.
Uterine cancer is the fourth most common cancer in women in the UK and mainly occurs in the seventh or eighth decade of life.
DNA in human cells accumulates mutations throughout a person's lifespan. Only a very small proportion of these mutations are harmful and contribute to the development of cancer. It usually takes three to six harmful 'driver mutations' for cancer to develop and the vast majority of cells with these mutations never turn cancerous.
The researchers from the Wellcome Sanger Institute, the University of Cambridge and their collaborators analysed healthy endometrial tissue donated by 28 women from the ages of 19 to 81 years to better understand genetic changes in healthy tissues. To do this, the researchers developed a technology with which they can sequence the genomes of a small number of cells from individual glands in the endometrial layer.
Laser-capture microscopy was used to isolate 292 endometrial glands from the endometrial tissue and whole-genome sequencing to detect changes in the DNA from each gland. By comparing the uterine DNA sequences to other healthy tissues from the same individual, it was possible to detect mutations in the uterine cells.
Co-author Dr Kourosh Saeb-Parsy from the University of Cambridge said 'Incidence of uterine cancers have been steadily rising in the UK for several decades, so knowing when and why genetic changes linked to cancer occur will be vital in helping to reverse this trend.'