{"entity":{"id":"paper-jones-pancreatic-core-pathways-science-2008","kind":"paper","name":"Core signaling pathways in human pancreatic cancers revealed by global genomic analyses","aka":[],"tldr":"The first complete reading of the protein-coding genes in 24 pancreatic cancers found an average of 63 changes per tumour that, however varied gene by gene, hit the same dozen cellular pathways in almost every case.","summary":"The sequences of 23,219 transcripts representing 20,661 protein-coding genes were determined in 24 pancreatic cancers, with SNP arrays for homozygous deletions and amplifications and next-generation transcriptome sequencing. Pancreatic cancers contained an average of 63 genetic alterations, mostly point mutations, defining a core set of 12 signalling pathways and processes each altered in 67 to 100% of tumours. The authors concluded that dysregulation of these core pathways can explain the major features of pancreatic tumorigenesis and that the pathways only become evident once coding regions are analysed in depth.","asOf":"2026-09-24","links":[{"label":"Jones et al., Science 2008: core signalling pathways in 24 pancreatic cancers","url":"https://doi.org/10.1126/science.1164368"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18772397/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":["kras","tp53","cdkn2a","smad4"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["pancreatic-cancer-signalling"],"terms":["driver-mutation"],"trials":[],"people":["bert-vogelstein","kenneth-kinzler","nickolas-papadopoulos","elizabeth-jaffee","anirban-maitra"],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2008,"doi":"10.1126/science.1164368","pmid":"18772397","authors":"Jones S, Zhang X, Parsons DW, et al.","paperType":"translational","findings":["Average of 63 genetic alterations per tumour, mostly point mutations.","Twelve core pathways and processes each altered in 67 to 100% of the 24 tumours."],"whatItMeans":"It set the frame that every later landscape paper filled in: pancreatic cancer is a disease of a few pathways broken by many different genes, so drugs must aim at pathways or their dependencies rather than one rare mutation.","caveats":["24 tumours, Sanger-era depth, no stromal correction.","Pathway membership was defined by the authors' curation."],"changedPractice":false,"participants":24},"route":"/key-papers/paper-jones-pancreatic-core-pathways-science-2008/","neighbours":{"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"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":"johns-hopkins","kind":"institution","name":"Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center","route":"/institutions/johns-hopkins/"}],"pathway":[{"id":"pancreatic-cancer-signalling","kind":"pathway","name":"Pancreatic cancer (KEGG map)","route":"/pathways/pancreatic-cancer-signalling/"}],"term":[{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"}],"person":[{"id":"anirban-maitra","kind":"person","name":"Anirban Maitra","route":"/people/anirban-maitra/"},{"id":"bert-vogelstein","kind":"person","name":"Bert Vogelstein","route":"/people/bert-vogelstein/"},{"id":"elizabeth-jaffee","kind":"person","name":"Elizabeth M. Jaffee","route":"/people/elizabeth-jaffee/"},{"id":"kenneth-kinzler","kind":"person","name":"Kenneth W. Kinzler","route":"/people/kenneth-kinzler/"},{"id":"nickolas-papadopoulos","kind":"person","name":"Nickolas Papadopoulos","route":"/people/nickolas-papadopoulos/"}],"journal":[{"id":"science","kind":"journal","name":"Science","route":"/journals/science/"}]}}