The landscape of somatic mutation in normal colorectal epithelial cells.
Level 4 - case-series / case-control
Cross-sectional genomic profiling of human tissue specimens (graded by design analogy).
PubMed 31645730 · doi:10.1038/s41586-019-1672-7
What was done
Whole-genome sequencing was performed on hundreds of individual normal colorectal crypts sampled from 42 individuals to characterize somatic mutations and mutational signatures in morphologically normal colorectal epithelium.
What was found
Signatures of multiple mutational processes were identified, including both ubiquitous/continuous processes and others restricted to specific individuals, crypts, or life periods. Probable driver mutations were identified in approximately 1% of normal colorectal crypts from middle-aged individuals. Colorectal cancers demonstrated substantially higher mutational burdens than normal cells, though specific numerical counts for mutational burdens were not reported in the abstract.
Why it matters
This study demonstrates that neoplastic somatic mutations and early clonal expansions are common in morphologically normal tissue, showing that adenomas and carcinomas represent rare endpoints of a widespread background evolutionary process.
Limits
The sample size is relatively small (42 individuals). The abstract does not provide exact total crypt counts, specific driver mutation types, or absolute mutational burden values, and the cross-sectional design cannot directly track the prospective neoplastic potential of mutated crypts.
Cited by
- supports Genetic sequencing of healthy individuals reveals driver gene mutations in normal cells that do not exhibit dysregulated cell growth.