For the first time, a group from Niigata University, Sasaki Institute, and National Institute of Genetics has elucidated the mechanism by which cancer-related gene mutations accumulate and spread in the human endometrium, which should repeat exfoliation and regeneration due to menstruation.
Previous studies have shown that pathologically "normal" endometrium already has cancer-related gene mutations.This time, a total of 32 endometrial ducts were collected from 891 research participants who seemed to have no abnormalities in the endometrium, and as a result of genome analysis, more than half of the ducts also had some kind of cancer-related gene mutation. Was.It was also found that the amount of mutation increased with aging and the cumulative number of menstrual periods.Furthermore, focusing on the types of mutations, it was found that gene mutations related to gynecologic cancer are subject to particularly strong positive natural selection pressure, and are recognized as mutations that are favorable for the survival of ducts.
Next, when the distribution of the ducts with the mutation was examined, it was found that the ducts having the same mutation formed clusters in the endometrium.This involved the rhizome structure of the glandular duct, which the group found in another previous study.When observing the three-dimensional structure of the endometrium, there is a reticulated rhizome structure in the glandular duct of the basal layer that remains unpeeled during menstruation.As a result of genome analysis of ducts sharing the same rhizome, all the populations had the same gene mutation profile.In other words, it is clear that even if the endometrium is peeled off with each menstruation, cancer-related gene mutations accumulate in the rhizome of the basal layer, and the mutant gland duct expands in the uterus via the rhizome. It became.
Due to late marriage and declining birthrate, the number of menstrual periods experienced in the life of modern women is increasing, and the number of women suffering from endometrium-related diseases is increasing accordingly.Based on the mechanism by which gene mutations spread in the endometrium, which was clarified in this study, it is expected to develop effective preventive methods for diseases related to the endometrium.
Paper information:[Nature Communications] Spatio temporary dynamics of clonal selection and diversification in normal endometrial epithelium
