{"entity":{"id":"paper-bailey-molecular-subtypes-pancreatic-nature-2016","kind":"paper","name":"Genomic analyses identify molecular subtypes of pancreatic cancer","aka":[],"tldr":"The 2016 analysis of 456 pancreatic cancers that grouped 32 recurrently mutated genes into ten pathways and defined four expression subtypes, of which the squamous type has the worst prognosis.","summary":"Bailey and colleagues of the Australian Pancreatic Cancer Genome Initiative integrated genomic analysis of 456 pancreatic ductal adenocarcinomas. Thirty-two recurrently mutated genes aggregated into ten pathways: KRAS, TGF-beta, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined four subtypes: squamous (enriched for TP53 and KDM6A mutations, TP63 network upregulation and hypermethylation of pancreatic endodermal cell-fate genes, with poor prognosis), pancreatic progenitor (FOXA2/3, PDX1, MNX1), immunogenic (upregulated immune networks including acquired immune suppression) and aberrantly differentiated endocrine exocrine (ADEX; KRAS activation, exocrine and endocrine differentiation networks). The subtypes correlate with histopathology and, the authors argue, identify opportunities for therapeutic development.","asOf":"2026-09-24","links":[{"label":"Nature 2016","url":"https://doi.org/10.1038/nature16965"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26909576/"},{"label":"cBioPortal study paad_qcmg_uq_2016 (QCMG, Nature 2016; 456 samples, 383 sequenced, no copy-number profile)","url":"https://www.cbioportal.org/study/summary?id=paad_qcmg_uq_2016"}],"tags":["pancreatic-evidence"],"related":["paper-waddell-whole-genomes-pancreatic-nature-2015","paper-moffitt-virtual-microdissection-subtypes-nat-genet-2015"],"cancers":["pancreatic"],"sections":[],"technologies":["wes-wgs","rna-seq"],"targets":["kras","tp53","kdm6a","smad4","cdkn2a","rnf43","arid1a"],"drugs":[],"companies":[],"institutions":["garvan-institute","beatson-glasgow"],"pathways":["ras-mapk","tgf-beta","ddr","pancreatic-cancer-signalling","wnt","notch","swi-snf-chromatin","epigenetic-reprogramming"],"terms":["somatic-mutations-wxs-wgs"],"trials":[],"people":["owen-sansom"],"bottlenecks":["b-tumor-heterogeneity"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2016,"doi":"10.1038/nature16965","pmid":"26909576","authors":"Bailey P, Chang DK, Nones K, et al.","paperType":"basic","findings":["456 tumours; 32 recurrently mutated genes in 10 pathways.","Four expression subtypes: squamous, pancreatic progenitor, immunogenic, ADEX.","Squamous tumours carry TP53 and KDM6A mutations and have poor prognosis."],"whatItMeans":"With Moffitt's classical and basal-like split (the squamous and basal-like groups overlap) this fixed the molecular vocabulary of the disease and gave Precision-Panc and the UK's Glasgow group their trial framework.","caveats":["The ADEX and immunogenic subtypes may partly reflect normal pancreas and immune cells in the sample rather than tumour biology.","Subtype has not yet been used to choose treatment in a positive randomised trial."],"participants":456},"route":"/key-papers/paper-bailey-molecular-subtypes-pancreatic-nature-2016/","neighbours":{"paper":[{"id":"paper-moffitt-virtual-microdissection-subtypes-nat-genet-2015","kind":"paper","name":"Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma","route":"/key-papers/paper-moffitt-virtual-microdissection-subtypes-nat-genet-2015/"},{"id":"paper-waddell-whole-genomes-pancreatic-nature-2015","kind":"paper","name":"Whole genomes redefine the mutational landscape of pancreatic cancer","route":"/key-papers/paper-waddell-whole-genomes-pancreatic-nature-2015/"}],"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"target":[{"id":"arid1a","kind":"target","name":"ARID1A","route":"/targets/arid1a/"},{"id":"cdkn2a","kind":"target","name":"CDKN2A","route":"/targets/cdkn2a/"},{"id":"kdm6a","kind":"target","name":"KDM6A","route":"/targets/kdm6a/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"rnf43","kind":"target","name":"RNF43","route":"/targets/rnf43/"},{"id":"smad4","kind":"target","name":"SMAD4","route":"/targets/smad4/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"institution":[{"id":"beatson-glasgow","kind":"institution","name":"Beatson West of Scotland Cancer Centre / CRUK Scotland Institute","route":"/institutions/beatson-glasgow/"},{"id":"garvan-institute","kind":"institution","name":"Garvan Institute of Medical Research / Kinghorn Cancer Centre","route":"/institutions/garvan-institute/"}],"pathway":[{"id":"ddr","kind":"pathway","name":"DNA damage response & homologous recombination","route":"/pathways/ddr/"},{"id":"epigenetic-reprogramming","kind":"pathway","name":"Epigenetic reprogramming","route":"/pathways/epigenetic-reprogramming/"},{"id":"notch","kind":"pathway","name":"Notch signalling","route":"/pathways/notch/"},{"id":"pancreatic-cancer-signalling","kind":"pathway","name":"Pancreatic cancer (KEGG map)","route":"/pathways/pancreatic-cancer-signalling/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"},{"id":"swi-snf-chromatin","kind":"pathway","name":"SWI/SNF chromatin remodelling","route":"/pathways/swi-snf-chromatin/"},{"id":"tgf-beta","kind":"pathway","name":"TGF-β signalling","route":"/pathways/tgf-beta/"},{"id":"wnt","kind":"pathway","name":"Wnt / β-catenin","route":"/pathways/wnt/"}],"term":[{"id":"somatic-mutations-wxs-wgs","kind":"term","name":"Somatic mutations from exome and genome sequencing (WXS, WGS)","route":"/terms/somatic-mutations-wxs-wgs/"}],"person":[{"id":"owen-sansom","kind":"person","name":"Owen Sansom","route":"/people/owen-sansom/"}],"bottleneck":[{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}],"journal":[{"id":"nature","kind":"journal","name":"Nature","route":"/journals/nature/"}],"roadmap":[{"id":"pancreatic-roadmap","kind":"roadmap","name":"Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question","route":"/roadmaps/pancreatic-roadmap/"}]}}