The mutational landscape of normal human endometrial epithelium.
Level 4 - case-series / case-control
Level 4 by design analogy: cross-sectional genomic sequencing study of human tissue samples.
PubMed 32350471 · doi:10.1038/s41586-020-2214-z
What was done
Whole-genome sequencing was performed on normal human endometrial glands to evaluate clonality, somatic mutation burden, mutational signatures, cancer driver mutations, and their associations with age and parity.
What was found
Normal human endometrial glands are clonal cell populations. Their total somatic mutation burden increases at a rate of approximately 29 base substitutions per year, which is many-fold lower than the mutation burden of endometrial cancers. Glands frequently harbor cancer driver mutations; the burden of these drivers increases with age and decreases with parity. Driver-bearing clones often arise during the first decades of life and progressively colonize the endometrial epithelial lining.
Why it matters
This study shows that neoplastic-like clonal evolution and cancer driver acquisition are widespread in physiologically normal human endometrium, beginning early in life and influenced by reproductive history.
Limits
The abstract does not disclose the sample size (number of donors or individual glands sequenced), donor age ranges, sequencing depth, or specific driver genes identified. It does not measure prospective risk of progression to cancer or functional impacts on endometrial function.
Cited by
- supports Genetic sequencing of healthy individuals reveals driver gene mutations in normal cells that do not exhibit dysregulated cell growth.