{"entity":{"id":"paper-lee-six-somatic-mutation-normal-colorectal-crypts-nature-2019","kind":"paper","name":"The landscape of somatic mutation in normal colorectal epithelial cells","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-24","links":[{"label":"Lee-Six et al., Nature 2019: whole genomes of hundreds of normal colorectal crypts from 42 people","url":"https://doi.org/10.1038/s41586-019-1672-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31645730/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["wes-wgs","single-cell-spatial"],"targets":["apc","kras"],"drugs":[],"companies":[],"institutions":[],"pathways":["field-cancerisation","clonal-evolution","mutagenesis-signatures"],"terms":["driver-mutation","mutational-signature","tmb"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2019,"doi":"10.1038/s41586-019-1672-7","pmid":"31645730","authors":"Lee-Six H, Olafsson S, Ellis P, et al.","paperType":"basic","findings":["Probable driver mutations in about 1% of normal colorectal crypts in middle age.","Multiple mutational processes, some universal and continuous, others individual or episodic.","Cancers carry substantially higher mutation burdens than normal crypts."],"whatItMeans":"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.","caveats":["42 individuals, mostly from surgical specimens.","Crypt-level whole-genome sequencing is laborious, so the sample of crypts per person is small."],"changedPractice":false,"participants":42},"route":"/key-papers/paper-lee-six-somatic-mutation-normal-colorectal-crypts-nature-2019/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"technology":[{"id":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","route":"/technologies/single-cell-spatial/"},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"target":[{"id":"apc","kind":"target","name":"APC","route":"/targets/apc/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"}],"pathway":[{"id":"clonal-evolution","kind":"pathway","name":"Clonal evolution & minimal residual disease","route":"/pathways/clonal-evolution/"},{"id":"field-cancerisation","kind":"pathway","name":"Field cancerisation","route":"/pathways/field-cancerisation/"},{"id":"mutagenesis-signatures","kind":"pathway","name":"Mutagenesis & mutational signatures","route":"/pathways/mutagenesis-signatures/"}],"term":[{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"},{"id":"mutational-signature","kind":"term","name":"Mutational signature","route":"/terms/mutational-signature/"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"}],"journal":[{"id":"nature","kind":"journal","name":"Nature","route":"/journals/nature/"}]}}