ArticleNature2018
Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes.
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Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 283 papers, 2 of them syntheses that pooled it.
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283citing papers in PubMed, 2 pooled it
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Who cites it
283 citing papers in PubMed, 2 syntheses or guidelines pooled it, 435 citations in OpenAlex.
- Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review.Signal transduction and targeted therapy · 2023Pooled it
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- THBS2/CA19-9 Detecting Pancreatic Ductal Adenocarcinoma at Diagnosis Underperforms in Prediagnostic Detection: Implications for Biomarker Advancement.Cancer prevention research (Philadelphia, Pa.) · 2021Trial
- The underexplored complexity of pancreatic cancer: Early dissemination and quiescence.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Biomarker discovery and patient stratification in pancreatic cancer using incomplete multi-omics data.PLoS computational biology · 2026Article
- Review
- KRAS signaling networks, mutational heterogeneity, and emerging therapeutic strategies for cancer treatment.Biomarker research · 2026Review
- Article
- Gene mutant dosage is associated with prognosis and metastatic tropism in 60,000 clinical cancer samples.Nature genetics · 2026Article
- Hypoxia-induced metastatic heterogeneity in pancreatic cancer.Nature communications · 2026Article
- Personalized reference genome-based pipeline reveals comprehensive haplotype-resolved views of cancer genomes.bioRxiv : the preprint server for biology · 2026Article
- Radioluminescence microscopy of tumor organoids enabled by a reconfigurable high-resolution imaging setup.EJNMMI research · 2026Article
- Inactivation of CDKN2AARF Promotes p53-Independent Remodeling of the PDAC Tumor Microenvironment.Cancer research · 2026Article
- Oncogenic KRAS-driven type I interferon signalling primes pancreatic cancer for necroptosis.Nature communications · 2026Article
- Review
- The Protein Phosphatase Inhibitor LB100 Targets the Mesenchymal Lineage of Pancreatic Ductal Adenocarcinoma.MedComm · 2026Article
- Inference of upstream-mutation and metabolomic-signature causality identifies prognostic biomarkers and therapeutic targets in pancreatic cancer.Nature communications · 2026Article
- GATA4 loss promotes mutantbioRxiv : the preprint server for biology · 2026Article
- Article
- Integrating single-cell and bulk transcriptomes to reveal prognostic and immunological features of ecDNA-related genes in osteosarcoma.Cancer immunology, immunotherapy : CII · 2026Article
223 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
50 authors at 10 institutions in 3 countries.
Sebastian MuellerCenter for Translational Cancer Research (TranslaTUM), Technische Universität München, 81675 Munich, Germany.
Thomas EngleitnerCenter for Translational Cancer Research (TranslaTUM), Technische Universität München, 81675 Munich, Germany.
Roman MareschCenter for Translational Cancer Research (TranslaTUM), Technische Universität München, 81675 Munich, Germany.
Magdalena ZukowskaCenter for Translational Cancer Research (TranslaTUM), Technische Universität München, 81675 Munich, Germany.
Sebastian LangeCenter for Translational Cancer Research (TranslaTUM), Technische Universität München, 81675 Munich, Germany.
Thorsten KaltenbacherCenter for Translational Cancer Research (TranslaTUM), Technische Universität München, 81675 Munich, Germany.
Björn KonukiewitzInstitute of Pathology, Technische Universität München, 81675 Munich, Germany.
Rupert ÖllingerCenter for Translational Cancer Research (TranslaTUM), Technische Universität München, 81675 Munich, Germany.
Maximilian ZwiebelDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Alex StrongThe Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Hsi-Yu YenGerman Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Ruby BanerjeeThe Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Sandra LouzadaThe Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Beiyuan FuThe Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Barbara SeidlerCenter for Translational Cancer Research (TranslaTUM), Technische Universität München, 81675 Munich, Germany.
Juliana GötzfriedDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Kathleen SchuckDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Zonera HassanDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Andreas ArbeiterDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Nina SchönhuberCenter for Translational Cancer Research (TranslaTUM), Technische Universität München, 81675 Munich, Germany.
Sabine KleinCenter for Translational Cancer Research (TranslaTUM), Technische Universität München, 81675 Munich, Germany.
Christian VeltkampCenter for Translational Cancer Research (TranslaTUM), Technische Universität München, 81675 Munich, Germany.
Mathias FriedrichThe Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Lena RadDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Maxim BarenboimDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Christoph ZiegenhainAnthropology & Human Genomics, Department of Biology II, Ludwig-Maximilians Universität, 82152 Martinsried, Germany.
Julia HessHelmholtz Zentrum München, Research Unit Radiation Cytogenetics, 85764 Neuherberg, Germany.
Oliver M DoveyThe Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Stefan EserDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Swati ParekhAnthropology & Human Genomics, Department of Biology II, Ludwig-Maximilians Universität, 82152 Martinsried, Germany.
Fernando Constantino-CasasDepartment of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
Jorge de la RosaThe Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Marta I SierraInstitute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, 33011 Oviedo, Spain.
Mario FragaInstitute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, 33011 Oviedo, Spain.
Julia MayerleMedizinische Klinik und Poliklinik II, Klinikum der LMU München-Grosshadern, 81377 Munich, Germany.
Günter KlöppelInstitute of Pathology, Technische Universität München, 81675 Munich, Germany.
Juan CadiñanosThe Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Pentao LiuThe Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
George VassiliouThe Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Wilko WeichertGerman Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Katja SteigerInstitute of Pathology, Technische Universität München, 81675 Munich, Germany.
Wolfgang EnardAnthropology & Human Genomics, Department of Biology II, Ludwig-Maximilians Universität, 82152 Martinsried, Germany.
Roland M SchmidDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Fengtang YangThe Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Kristian UngerHelmholtz Zentrum München, Research Unit Radiation Cytogenetics, 85764 Neuherberg, Germany.
Günter SchneiderDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Ignacio VarelaInstituto de Biomedicina y Biotecnología de Cantabria (UC-CSIC), 39012 Santander, Spain.
Allan BradleyThe Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Dieter SaurCenter for Translational Cancer Research (TranslaTUM), Technische Universität München, 81675 Munich, Germany.
Roland RadCenter for Translational Cancer Research (TranslaTUM), Technische Universität München, 81675 Munich, Germany.
Technical University of Munich · DEWellcome Sanger Institute · GBKlinikum rechts der Isar · DEGerman Cancer Research Center · DELudwig-Maximilians-Universität München · DEUniversidad de Oviedo · ESHeidelberg University · DEHelmholtz Zentrum München · DEInstituto de Biomedicina y Biotecnología de Cantabria · ESUniversity of Cambridge · GB
Funding
Cancer Research UK 23015European Research Council 648521Medical Research Council MC_PC_12009
Abstract
The poor correlation of mutational landscapes with phenotypes limits our understanding of the pathogenesis and metastasis of pancreatic ductal adenocarcinoma (PDAC). Here we show that oncogenic dosage-variation has a critical role in PDAC biology and phenotypic diversification. We find an increase in gene dosage of mutant KRAS in human PDAC precursors, which drives both early tumorigenesis and metastasis and thus rationalizes early PDAC dissemination. To overcome the limitations posed to gene dosage studies by the stromal richness of PDAC, we have developed large cell culture resources of metastatic mouse PDAC. Integration of cell culture genomes, transcriptomes and tumour phenotypes with functional studies and human data reveals additional widespread effects of oncogenic dosage variation on cell morphology and plasticity, histopathology and clinical outcome, with the highest Kras
Indexed as
Evolution, MolecularGene DosageAdaptor Proteins, Signal TransducingAllelesAnimalsCarcinogenesisCarcinoma, Pancreatic DuctalCell Cycle ProteinsCyclin-Dependent Kinase Inhibitor p16Disease ProgressionFemaleGenes, mycGenes, p53HumansMaleMiceAdaptor Proteins, Signal TransducingCdkn2a protein, mouseCell Cycle ProteinsCyclin-Dependent Kinase Inhibitor p16Hras protein, mouseKRAS protein, humanNF-kappa B p52 SubunitNFKB2 protein, humanNfkb2 protein, mouseNuclear ProteinsPhosphoproteinsProto-Oncogene Proteins p21(ras)Transcription FactorsTransforming Growth Factor beta1Yap1 protein, mouseYAP-Signaling ProteinsYY1AP1 protein, human
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