{"entity":{"id":"paper-qian-driver-genes-outcomes-resected-pancreatic-jama-oncol-2018","kind":"paper","name":"Association of alterations in main driver genes with outcomes of patients with resected pancreatic ductal adenocarcinoma","aka":[],"tldr":"In 356 patients whose pancreatic cancer was removed, the more of the four main driver genes were broken the worse the outcome, KRAS G12D was the worst allele, CDKN2A loss shortened survival, and SMAD4 status made no difference.","summary":"KRAS, CDKN2A, SMAD4 and TP53 were assessed by immunohistochemistry and next-generation sequencing in 356 resected pancreatic adenocarcinomas from Dana-Farber/Brigham, Rochester and Stanford. KRAS-mutant tumours had worse disease-free (12.3 versus 16.2 months) and overall survival (20.3 versus 38.6 months; 5-year 13.0% versus 30.2%) than wild-type; KRAS G12D carried median overall survival 15.3 months. Loss of CDKN2A expression gave disease-free survival 11.5 versus 14.8 and overall survival 19.7 versus 24.6 months. SMAD4 status was not associated with outcome; TP53 only with shorter disease-free survival (hazard ratio 1.33). Four altered genes against 0 to 2 gave a disease-free survival hazard ratio of 1.79; 5-year overall survival 18.4%, 14.1% and 8.2% for 0 to 2, 3 and 4 alterations.","asOf":"2026-09-24","links":[{"label":"Qian et al., JAMA Oncol 2018: the four driver genes and outcome in 356 resected cancers","url":"https://doi.org/10.1001/jamaoncol.2017.3420"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29098284/"}],"tags":[],"related":["kras-g12d"],"cancers":["pancreatic","resectable-pdac"],"sections":[],"technologies":[],"targets":["kras","cdkn2a","smad4","tp53"],"drugs":[],"companies":[],"institutions":["dana-farber","stanford"],"pathways":["p53-cell-cycle","ras-mapk"],"terms":["kras-mutation-subtypes"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2018,"doi":"10.1001/jamaoncol.2017.3420","pmid":"29098284","authors":"Qian ZR, Rubinson DA, Nowak JA, et al.","paperType":"observational","findings":["KRAS wild-type: overall survival 38.6 versus 20.3 months; G12D 15.3 months.","CDKN2A loss: overall survival 19.7 versus 24.6 months; SMAD4 not prognostic; TP53 disease-free only.","Four altered drivers: 5-year survival 8.2% versus 18.4%."],"whatItMeans":"The driver count is a prognostic score in itself, and the allele matters: G12D is the pancreatic allele with the worst outlook and the one the new selective inhibitors chase.","caveats":["Retrospective, three centres, mixed perioperative treatment.","SMAD4's metastatic-pattern effect (Iacobuzio-Donahue 2009) did not show as a survival difference here."],"changedPractice":false,"participants":356},"route":"/key-papers/paper-qian-driver-genes-outcomes-resected-pancreatic-jama-oncol-2018/","neighbours":{"biomarker":[{"id":"kras-g12d","kind":"biomarker","name":"KRAS G12D (and other non-G12C KRAS mutations)","route":"/biomarkers/kras-g12d/"}],"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"resectable-pdac","kind":"cancer","name":"Resectable pancreatic ductal adenocarcinoma","route":"/cancers/resectable-pdac/"}],"target":[{"id":"cdkn2a","kind":"target","name":"CDKN2A","route":"/targets/cdkn2a/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"smad4","kind":"target","name":"SMAD4","route":"/targets/smad4/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"institution":[{"id":"dana-farber","kind":"institution","name":"Dana-Farber Brigham Cancer Center","route":"/institutions/dana-farber/"},{"id":"stanford","kind":"institution","name":"Stanford Health Care / Stanford Cancer Institute","route":"/institutions/stanford/"}],"pathway":[{"id":"p53-cell-cycle","kind":"pathway","name":"p53 / RB / cell-cycle checkpoint","route":"/pathways/p53-cell-cycle/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"term":[{"id":"kras-mutation-subtypes","kind":"term","name":"KRAS mutation subtypes (G12C, G12D, G12V)","route":"/terms/kras-mutation-subtypes/"}],"journal":[{"id":"jama-oncology","kind":"journal","name":"JAMA Oncology","route":"/journals/jama-oncology/"}]}}