Somatic mutant clones colonize the human esophagus with age.
Level 4 - case-series / case-control
Cross-sectional post-mortem/donor tissue genomic analysis (n = 9).
PubMed 30337457 · doi:10.1126/science.aau3879
What was done
Genome sequencing was performed on normal esophageal epithelium samples collected from 9 human donors aged 20 to 75 years to map the accumulation and clonal expansion of somatic mutations across the lifespan.
What was found
Somatic mutations accumulated with age, predominantly via intrinsic mutational processes. There was strong positive selection for clones carrying mutations in 14 cancer genes, reaching tens to hundreds of clones per square centimeter. In middle-aged and elderly donors, clones carrying cancer-associated mutations covered much of the epithelium: NOTCH1 mutations affected 12% to 80% of cells, and TP53 mutations affected 2% to 37% of cells. The prevalence of NOTCH1 mutations in normal tissue was several times higher than in esophageal cancers.
Why it matters
This study shows that normal aging human esophagus is heavily colonized by clones bearing classic oncogenic mutations, shifting understanding of the baseline genomic landscape of healthy aging tissue.
Limits
The sample size is very small (n = 9 donors), limiting demographic and risk factor stratification. The abstract does not detail donor medical histories or exposures, nor does it provide longitudinal follow-up on cancer progression.
Cited by
- supports By age 40, people generally have precancerous cells with genetic mutations.