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Reading the whole genome of hundreds of individual healthy bowel glands from 42 people found that about one in a hundred already carries a cancer-driving mutation by middle age. Polyps and cancers are the rare survivors of a process happening everywhere in the bowel lining.
Whole-genome sequencing was used to analyse hundreds of normal crypts from 42 individuals. Signatures of multiple mutational processes were revealed: some ubiquitous and continuous, others found only in some individuals, in some crypts or during certain periods of life. Probable driver mutations were present in around 1% of normal colorectal crypts in middle-aged individuals, indicating that adenomas and carcinomas are rare outcomes of a pervasive process of neoplastic change across morphologically normal colorectal epithelium. Colorectal cancers showed substantially increased mutational burdens relative to normal cells.
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.
Shares Mutational signature, Tumour mutational burden (TMB), Whole-exome & whole-genome sequencing.
Shares APC, Driver mutation, Clonal evolution & minimal residual disease, KRAS.
Shares Clonal evolution & minimal residual disease, Nature, Whole-exome & whole-genome sequencing.
Shares APC, Driver mutation, KRAS, Colorectal cancer.
Shares APC, Mutational signature, Colorectal cancer.
Shares Clonal evolution & minimal residual disease, Nature, Whole-exome & whole-genome sequencing, KRAS.
Shares APC, Nature, Whole-exome & whole-genome sequencing, Colorectal cancer.