# Genomic analyses identify molecular subtypes of pancreatic cancer

Source: https://onco.cc/key-papers/paper-bailey-molecular-subtypes-pancreatic-nature-2016/  
OnCo record `paper-bailey-molecular-subtypes-pancreatic-nature-2016` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: pancreatic-evidence
- Journal: Nature
- Year: 2016
- DOI: 10.1038/nature16965
- Authors: Bailey P, Chang DK, Nones K, et al.
- 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.
- What it means: 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.

## Sources

- Nature 2016: https://doi.org/10.1038/nature16965
- PubMed: https://pubmed.ncbi.nlm.nih.gov/26909576/
- cBioPortal study paad_qcmg_uq_2016 (QCMG, Nature 2016; 456 samples, 383 sequenced, no copy-number profile): https://www.cbioportal.org/study/summary?id=paad_qcmg_uq_2016

## Connected records

- key papers: [Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma](https://onco.cc/key-papers/paper-moffitt-virtual-microdissection-subtypes-nat-genet-2015/), [Whole genomes redefine the mutational landscape of pancreatic cancer](https://onco.cc/key-papers/paper-waddell-whole-genomes-pancreatic-nature-2015/)
- cancers: [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [RNA sequencing & expression profiling](https://onco.cc/technologies/rna-seq/), [Whole-exome & whole-genome sequencing](https://onco.cc/technologies/wes-wgs/)
- targets: [ARID1A](https://onco.cc/targets/arid1a/), [CDKN2A](https://onco.cc/targets/cdkn2a/), [KDM6A](https://onco.cc/targets/kdm6a/), [KRAS](https://onco.cc/targets/kras/), [RNF43](https://onco.cc/targets/rnf43/), [SMAD4](https://onco.cc/targets/smad4/), [TP53](https://onco.cc/targets/tp53/)
- institutions: [Beatson West of Scotland Cancer Centre / CRUK Scotland Institute](https://onco.cc/institutions/beatson-glasgow/), [Garvan Institute of Medical Research / Kinghorn Cancer Centre](https://onco.cc/institutions/garvan-institute/)
- pathways: [DNA damage response & homologous recombination](https://onco.cc/pathways/ddr/), [Epigenetic reprogramming](https://onco.cc/pathways/epigenetic-reprogramming/), [Notch signalling](https://onco.cc/pathways/notch/), [Pancreatic cancer (KEGG map)](https://onco.cc/pathways/pancreatic-cancer-signalling/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [SWI/SNF chromatin remodelling](https://onco.cc/pathways/swi-snf-chromatin/), [TGF-β signalling](https://onco.cc/pathways/tgf-beta/), [Wnt / β-catenin](https://onco.cc/pathways/wnt/)
- terms: [Somatic mutations from exome and genome sequencing (WXS, WGS)](https://onco.cc/terms/somatic-mutations-wxs-wgs/)
- people: [Owen Sansom](https://onco.cc/people/owen-sansom/)
- bottlenecks: [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)
- journals: [Nature](https://onco.cc/journals/nature/)
- roadmaps: [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/)

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