{"entity":{"id":"paper-chan-seng-yue-pancreatic-transcription-phenotypes-nat-genet-2020","kind":"paper","name":"Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution","aka":[],"tldr":"Whole genomes and transcriptomes from purified tumour cells showed that the classical and basal-like types are not two boxes but a continuum of mixed cell populations, set by how many copies of mutant KRAS and GATA6 a tumour has gained, often after its genome doubled.","summary":"A dataset of whole genomes and transcriptomes was generated from purified epithelium of primary and metastatic pancreatic adenocarcinomas. Transcriptome analysis demonstrated that molecular subtypes are a product of a gene expression continuum driven by a mixture of intratumoural subpopulations, confirmed by single-cell analysis. Integrated whole-genome analysis linked subtypes to specific copy-number aberrations in genes such as mutant KRAS and GATA6. Mapping tumour genetic histories identified tetraploidisation as a key mutational process behind these events.","asOf":"2026-09-24","links":[{"label":"Chan-Seng-Yue et al., Nat Genet 2020: transcription phenotypes driven by genomic events (purified whole genomes)","url":"https://doi.org/10.1038/s41588-019-0566-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31932696/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["wes-wgs","rna-seq","single-cell-spatial"],"targets":["kras"],"drugs":[],"companies":[],"institutions":["oicr","princess-margaret","cold-spring-harbor"],"pathways":["chromosomal-instability","clonal-evolution"],"terms":["whole-genome-doubling","copy-number-variation-term"],"trials":[],"people":["david-tuveson"],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2020,"doi":"10.1038/s41588-019-0566-9","pmid":"31932696","authors":"Chan-Seng-Yue M, Kim JC, Wilson GW, et al.","paperType":"translational","findings":["Subtypes are a continuum of intratumoural subpopulations, confirmed by single-cell analysis.","Mutant KRAS and GATA6 copy number drive the phenotype; tetraploidisation underlies the events."],"whatItMeans":"It explains why single-sample classifiers disagree on about one tumour in eight and why KRAS allelic imbalance and GATA6 copy number are being read alongside expression.","caveats":["Purified-epithelium cohort from one programme.","Clinical value of allele-dosage readouts is untested."],"changedPractice":false},"route":"/key-papers/paper-chan-seng-yue-pancreatic-transcription-phenotypes-nat-genet-2020/","neighbours":{"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":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","route":"/technologies/single-cell-spatial/"},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"target":[{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"}],"institution":[{"id":"cold-spring-harbor","kind":"institution","name":"Cold Spring Harbor Laboratory","route":"/institutions/cold-spring-harbor/"},{"id":"oicr","kind":"institution","name":"Ontario Institute for Cancer Research","route":"/institutions/oicr/"},{"id":"princess-margaret","kind":"institution","name":"Princess Margaret Cancer Centre","route":"/institutions/princess-margaret/"}],"pathway":[{"id":"chromosomal-instability","kind":"pathway","name":"Chromosomal instability & aneuploidy","route":"/pathways/chromosomal-instability/"},{"id":"clonal-evolution","kind":"pathway","name":"Clonal evolution & minimal residual disease","route":"/pathways/clonal-evolution/"}],"term":[{"id":"compass-study-pancreatic","kind":"term","name":"COMPASS: real-time sequencing of advanced pancreatic cancer for treatment selection","route":"/terms/compass-study-pancreatic/"},{"id":"copy-number-variation-term","kind":"term","name":"Copy number alteration (CNA)","route":"/terms/copy-number-variation-term/"},{"id":"gata6-classical-basal-marker","kind":"term","name":"GATA6 as the marker of classical versus basal-like pancreatic cancer","route":"/terms/gata6-classical-basal-marker/"},{"id":"kras-allelic-imbalance","kind":"term","name":"KRAS allelic imbalance and mutant KRAS dosage in pancreatic cancer","route":"/terms/kras-allelic-imbalance/"},{"id":"whole-genome-doubling","kind":"term","name":"Whole-genome doubling (WGD)","route":"/terms/whole-genome-doubling/"}],"person":[{"id":"david-tuveson","kind":"person","name":"David A. Tuveson","route":"/people/david-tuveson/"}],"journal":[{"id":"nature-genetics","kind":"journal","name":"Nature Genetics","route":"/journals/nature-genetics/"}]}}