{"entity":{"id":"paper-makohon-moore-metastases-driver-homogeneity-nat-genet-2017","kind":"paper","name":"Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer","aka":[],"tldr":"Deep sequencing of 26 separate metastases from four patients found the same driver mutations in every one, so a biopsy of any single site should represent the whole disease for targeted therapy.","summary":"Sixty-fold whole-genome sequencing of 26 metastases from four patients with pancreatic cancer showed identical mutations in known driver genes in every metastatic lesion for each patient. Passenger mutations accounted for all intratumoural heterogeneity, and even among those the genetic similarity of founding cells was higher than expected for two randomly chosen normal cells.","asOf":"2026-09-24","links":[{"label":"Makohon-Moore et al., Nat Genet 2017: limited driver heterogeneity among 26 metastases from four patients","url":"https://doi.org/10.1038/ng.3764"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28092682/"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":["wes-wgs"],"targets":[],"drugs":[],"companies":[],"institutions":["mskcc","johns-hopkins"],"pathways":["clonal-evolution"],"terms":[],"trials":[],"people":["bert-vogelstein"],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2017,"doi":"10.1038/ng.3764","pmid":"28092682","authors":"Makohon-Moore AP, Zhang M, Reiter JG, et al.","paperType":"translational","findings":["Identical driver mutations in all 26 metastases across four patients.","Heterogeneity was confined to passenger mutations."],"whatItMeans":"Encouraging for targeted therapy: unlike some cancers, the drivers do not differ between deposits, so one biopsy is enough to choose a RAS or repair-directed drug.","caveats":["Four patients from a rapid autopsy programme.","Treatment-naive metastases; therapy can add resistance mutations."],"changedPractice":false,"participants":4},"route":"/key-papers/paper-makohon-moore-metastases-driver-homogeneity-nat-genet-2017/","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":"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/"},{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"pathway":[{"id":"clonal-evolution","kind":"pathway","name":"Clonal evolution & minimal residual disease","route":"/pathways/clonal-evolution/"}],"person":[{"id":"bert-vogelstein","kind":"person","name":"Bert Vogelstein","route":"/people/bert-vogelstein/"}],"journal":[{"id":"nature-genetics","kind":"journal","name":"Nature Genetics","route":"/journals/nature-genetics/"}]}}