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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.
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.
Lung cancer in never-smokers is not smokers' lung cancer with the smoking removed; it is a different set of diseases with a different clock. The slow-growing piano subtype in particular is the argument that a screening test aimed at never-smokers would need to look for something other than what low-dose computed tomography was built to find.
It sets the baseline the adenoma-carcinoma sequence starts from and warns against reading a driver mutation found in tissue, or in stool or blood, as evidence of cancer.
One pathway page and one term page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
Carrying a cancer mutation is normal; most mutant clones never become cancer. This means blood or tissue tests that look for driver mutations alone will produce false positives, and that the question of what tips a mutant clone into cancer (tissue environment, further hits, immune surveillance) is as important as the mutation itself.
Shares Genomic and evolutionary classification of lung cancer in never smokers, The Francis Crick Institute, Theories of cancer: how the ideas connect, Clonal evolution & minimal residual disease and the tag mechanism.
Shares The Francis Crick Institute, Theories of cancer: how the ideas connect, Clonal evolution & minimal residual disease, Epigenetic reprogramming and the tag mechanism.
Shares Ageing tissue and clonal fields: cancer as a disease of old tissue, Theories of cancer: how the ideas connect, Clonal evolution & minimal residual disease, Epigenetic reprogramming and the tag mechanism.
Shares Martincorena: normal sun-exposed skin is a patchwork of cancer-mutation clones, NOTCH1, Head and neck squamous cell carcinoma, Non-small-cell lung cancer and the tag mechanism.
Shares The Francis Crick Institute, TP53, Colorectal cancer and the tag mechanism.
Shares Ageing tissue and clonal fields: cancer as a disease of old tissue, TP53 and the tag mechanism.
Shares The Francis Crick Institute, Theories of cancer: how the ideas connect and the tag mechanism.
Shares Epigenetic reprogramming, Colorectal cancer, Non-small-cell lung cancer and the tag mechanism.