Somatic Mutation: What Shapes the Mutational Landscape of Normal Epithelia?
Joanna C FowlerPhilip H JonesPublished in: Cancer discovery (2022)
Recent advances in sequencing have found somatic mutations in all epithelial tissues studied to date. Here we review how the mutational landscape of normal epithelia is shaped by clonal competition within the stem cell niche combined with environmental exposures. Some of the selected mutant genes are oncogenic, whereas others may be inhibitory of transformation. Discoveries in this area leave many open questions, such as the definition of cancer driver genes, the mechanisms by which tissues constrain a high proportion of oncogenic mutant cells, and whether clonal fitness can be modulated to decrease cancer risk.
Keyphrases
- stem cells
- single cell
- genome wide
- induced apoptosis
- gene expression
- copy number
- transcription factor
- genome wide identification
- papillary thyroid
- bioinformatics analysis
- wild type
- physical activity
- cell cycle arrest
- minimally invasive
- body composition
- squamous cell
- genome wide analysis
- squamous cell carcinoma
- signaling pathway
- human health
- endoplasmic reticulum stress
- mesenchymal stem cells
- bone marrow
- lymph node metastasis
- life cycle