Field cancerisation
Cancer often arises from a whole region of tissue that already carries mutations, not from one rogue cell. Sun-exposed skin, smokers' airways, and Barrett's oesophagus are patchworks of mutant clones competing long before a tumour appears.
Deep sequencing of normal tissue shows that by middle age, sun-exposed skin, oesophagus (NOTCH1, TP53), bronchial epithelium, endometrium, and colon crypts are colonised by clones carrying cancer-driver mutations, most of which never progress. Field effects explain second primary tumours and local recurrence after resection, and they define who benefits from interception (chemoprevention, surveillance). Clonal competition can even be protective (NOTCH1-mutant oesophageal clones outcompete TP53 clones). Understanding the transition from field to tumour is the central question for early detection and prevention.
In one picture
A lawn where many patches have already turned to weeds. Any single tumour is one patch that took over; mowing it leaves the rest of the lawn ready to sprout again.
Diagram
top- Surveillance and ablation of precancer (Barrett's RFA, cervical precancer ablation, colon polypectomy)
- Chemoprevention (aspirin in Lynch, tamoxifen, HPV vaccination)
- Field-directed therapy after resection (e.g., 5-FU cream for actinic keratosis)
- Molecular monitoring of fields (cytosponge, sputum, urine)
Notes
top- Leading programmes: Jones (Wellcome Sanger) on clones in normal oesophagus and skin; Campbell/Stratton (Sanger) on somatic mutation in normal tissues; Fitzgerald (Cambridge/CRUK) on Barrett's interception; Hopkins on field cancerisation in head and neck.
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