{"entity":{"id":"paper-yachida-metastasis-late-genetic-evolution-pancreatic-nature-2010","kind":"paper","name":"Distant metastasis occurs late during the genetic evolution of pancreatic cancer","aka":[],"tldr":"Comparing the genomes of primary tumours and their metastases put numbers on the timeline: about ten years from the first mutation to a fully formed tumour, five more before it can spread, and two years of life after that, so there is a long window in which the cancer could be caught.","summary":"The genomes of seven pancreatic cancer metastases were sequenced to evaluate clonal relationships among primary and metastatic cancers. Clonal populations giving rise to distant metastases were represented within the primary carcinoma but were genetically evolved from the original parental non-metastatic clone, so the genetic heterogeneity of metastases reflects that within the primary. Quantitative analysis indicated at least a decade between the initiating mutation and the birth of the parental non-metastatic founder cell, at least five more years for metastatic ability, and death an average of two years thereafter.","asOf":"2026-09-24","links":[{"label":"Yachida et al., Nature 2010: distant metastasis occurs late in the genetic evolution","url":"https://doi.org/10.1038/nature09515"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20981102/"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":["wes-wgs","pancreatic-surveillance"],"targets":[],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["clonal-evolution","metastatic-cascade"],"terms":[],"trials":[],"people":["bert-vogelstein","kenneth-kinzler"],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2010,"doi":"10.1038/nature09515","pmid":"20981102","authors":"Yachida S, Jones S, Bozic I, et al.","paperType":"translational","findings":["At least a decade from initiating mutation to the parental non-metastatic clone.","At least five more years to metastatic ability; death about two years later."],"whatItMeans":"It is the quantitative case for early detection: the biology allows a fifteen-year window, and the disease is lethal because we look too late, not because it moves fast.","caveats":["Seven patients and a mathematical model with assumptions about mutation rate.","Later work argues evolution is punctuated rather than steady (Notta 2016)."],"changedPractice":false,"participants":7},"route":"/key-papers/paper-yachida-metastasis-late-genetic-evolution-pancreatic-nature-2010/","neighbours":{"cancer":[{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"pancreatic-surveillance","kind":"technology","name":"High-risk pancreatic surveillance (CAPS / PRECEDE)","route":"/technologies/pancreatic-surveillance/"},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"institution":[{"id":"johns-hopkins","kind":"institution","name":"Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center","route":"/institutions/johns-hopkins/"}],"pathway":[{"id":"clonal-evolution","kind":"pathway","name":"Clonal evolution & minimal residual disease","route":"/pathways/clonal-evolution/"},{"id":"metastatic-cascade","kind":"pathway","name":"The metastatic cascade","route":"/pathways/metastatic-cascade/"}],"person":[{"id":"bert-vogelstein","kind":"person","name":"Bert Vogelstein","route":"/people/bert-vogelstein/"},{"id":"kenneth-kinzler","kind":"person","name":"Kenneth W. Kinzler","route":"/people/kenneth-kinzler/"}],"journal":[{"id":"nature","kind":"journal","name":"Nature","route":"/journals/nature/"}]}}