# Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution

Source: https://onco.cc/key-papers/paper-chan-seng-yue-pancreatic-transcription-phenotypes-nat-genet-2020/  
OnCo record `paper-chan-seng-yue-pancreatic-transcription-phenotypes-nat-genet-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Nature Genetics
- Year: 2020
- DOI: 10.1038/s41588-019-0566-9
- Authors: Chan-Seng-Yue M, Kim JC, Wilson GW, et al.
- 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.
- What it means: 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.

## Sources

- Chan-Seng-Yue et al., Nat Genet 2020: transcription phenotypes driven by genomic events (purified whole genomes): https://doi.org/10.1038/s41588-019-0566-9
- PubMed: https://pubmed.ncbi.nlm.nih.gov/31932696/

## Connected records

- cancers: [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [RNA sequencing & expression profiling](https://onco.cc/technologies/rna-seq/), [Single-cell & spatial profiling](https://onco.cc/technologies/single-cell-spatial/), [Whole-exome & whole-genome sequencing](https://onco.cc/technologies/wes-wgs/)
- targets: [KRAS](https://onco.cc/targets/kras/)
- institutions: [Cold Spring Harbor Laboratory](https://onco.cc/institutions/cold-spring-harbor/), [Ontario Institute for Cancer Research](https://onco.cc/institutions/oicr/), [Princess Margaret Cancer Centre](https://onco.cc/institutions/princess-margaret/)
- pathways: [Chromosomal instability & aneuploidy](https://onco.cc/pathways/chromosomal-instability/), [Clonal evolution & minimal residual disease](https://onco.cc/pathways/clonal-evolution/)
- terms: [COMPASS: real-time sequencing of advanced pancreatic cancer for treatment selection](https://onco.cc/terms/compass-study-pancreatic/), [Copy number alteration (CNA)](https://onco.cc/terms/copy-number-variation-term/), [GATA6 as the marker of classical versus basal-like pancreatic cancer](https://onco.cc/terms/gata6-classical-basal-marker/), [KRAS allelic imbalance and mutant KRAS dosage in pancreatic cancer](https://onco.cc/terms/kras-allelic-imbalance/), [Whole-genome doubling (WGD)](https://onco.cc/terms/whole-genome-doubling/)
- people: [David A. Tuveson](https://onco.cc/people/david-tuveson/)
- journals: [Nature Genetics](https://onco.cc/journals/nature-genetics/)

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