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Whole-genome DNA sequencing studies of normal endometrial glandulartissue have revealed the frequent presence of somatic driver mutations in cancer-relatedgenes. These findings were published in Nature.

While the acquisition of mutations overtime is believed to be a characteristic of all somatic cells, data are limitedon how it occurs in normal tissues.Nevertheless, the study authors noted that [t]he characterizationof the mutational landscapes of normal tissues isadvancing our understanding of the succession of intermediate neoplastic stages between normalcells and the cancers that originate fromthem.

One of the rationales for focusing on theendometrium of the uterus was related to its highly dynamic physiology duringthe reproductive years in response to fluctuating hormone levels, as well asits composition of stromal cells covered by a surface epithelium that iscontiguous with embedded glandular epithelium. Although the contiguity of thesurface epithelial sheet and the glandular tissue is disrupted duringmenstruation, it is subsequently restored by stem cells within retained embeddedglands.

In this study, 292 normal endometrialglands were isolated using laser-capture microdissection from 28 women between theages of 19 and 81 years. Comparisons of whole-exome DNA sequencing results forthese tissues with matched specimens of other types of normal tissue from thesame individual were used to identify somatic mutations in the endometrialglandular tissue. Corresponding data on patient age and parity allowed for theexploration of these factors on the rate and timing of somatic driver mutationsin normal glandular tissue of the endometrium.

Some of the keyfindings of this study included the following:

In their concluding remarks, the study authors noted that their results show that mutational landscapes differ markedly between normal tissues perhaps shaped by differences in their structure and physiology and indicate that the procession of neoplastic change that leads to endometrial cancer is initiated early in life.

Reference

Moore L, Leongamornlert D, Coorens THH, et al. The mutational landscape of normal human endometrial epithelium [published online April 22, 2020]. Nature. doi: 10.1038/s41586-020-2214-z

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Somatic Driver Mutations Leading to Endometrial Cancer Occur Early in Life - Cancer Therapy Advisor