An insight into the earliest stages of uterine cancer has been revealed after British scientists discovered cancer-driving mutations that often arise early in life.
Researchers at the Wellcome Sanger Institute, the University of Cambridge, UK, and collaborators conducted whole-genome sequencing of healthy human endometrium, to provide a comprehensive overview of the rates and patterns of DNA changes in this tissue.
The researchers developed technology to sequence the genomes of small numbers of cells from individual glands in the endometrial epithelium
They used laser-capture microscopy to isolate 292 endometrial glands from womb tissue samples that were donated by 28 women aged 19 to 81 years, before DNA from each gland was whole-genome sequenced.
The team then searched for somatic mutations in each gland by comparing them with whole genome sequences from other tissues from the same individuals.
Writing in the latest edition of Nature last night, they said they found that a high proportion of cells carried driver mutations, even though they appeared normal under the microscope. Many of these driver mutations appear to have arisen early in life, in many cases during childhood.
Lead researcher Dr Luiza Moore, of the Wellcome Sanger Institute, said: “Human endometrium is a highly dynamic tissue that undergoes numerous cycles of remodelling during female reproductive years. We identified frequent cancer driver mutations in normal endometrium and showed that many such events had occurred early in life, in some cases even before adolescence. Over time, these mutant stem cells accumulate further driver mutations.”
Dr Kourosh Saeb-Parsy, of the University of Cambridge and Director of the Cambridge Biorepository for Translational Medicine (CBTM), added: “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. This research is an important step and wouldn’t have been possible without the individuals who gifted precious samples for this study, including transplant donors and their families.”
Moore L, Leongamornlert D and Coorens THH et al. The mutational landscape of normal human endometrial epithelium. Nature 22 April 2020; doi: 10.1038/s41586-020-2214-z
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