Clonal Evolution in Healthy and Premalignant Tissues: Implications for Early Cancer Interception Strategies.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic and observational concepts without systematic review methodology or new human data.
PubMed 36930945 · doi:10.1158/1940-6207.CAPR-22-0469
What was done
This narrative review examines published evidence on the mutational landscape, single-nucleotide variation burden, and clonal dynamics across histologically normal, aging, and premalignant human somatic tissues, alongside microenvironmental factors such as stromal and immune co-evolution.
What was found
The abstract reports no numerical data. Qualitatively, it reports that histologically normal human tissues accumulate substantial mutational burdens with age across proliferating, post-mitotic, stem, and differentiated cell types. Clones under positive selection can expand widely across tissue surfaces, but the presence of these mutations alone is a poor predictor of subsequent malignant transformation in solid tissues, and common clonal mutations in normal tissue do not reliably mirror early driver mutations in corresponding cancers.
Why it matters
Demonstrating that somatic clonal expansions are widespread in healthy aging tissues shows that detecting mutations in isolation is insufficient for early cancer risk stratification. Effective cancer interception will require identifying the specific microenvironmental and cell-intrinsic selective determinants of transformation.
Limits
As a narrative review, the paper provides no original empirical datasets, clinical trial data, or systematic search methodology. The abstract provides no quantitative mutation frequencies, tissue-specific effect sizes, or participant sample sizes.
Cited by
- context Every person has cancer cells continuously present in their body that the immune system constantly destroys.