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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.
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.
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.
Shares KRAS allelic imbalance and mutant KRAS dosage in pancreatic cancer, Whole-genome doubling (WGD), Ontario Institute for Cancer Research, Chromosomal instability & aneuploidy.
Shares COMPASS: real-time sequencing of advanced pancreatic cancer for treatment selection, GATA6 as the marker of classical versus basal-like pancreatic cancer, Ontario Institute for Cancer Research, Princess Margaret Cancer Centre.
Shares COMPASS: real-time sequencing of advanced pancreatic cancer for treatment selection, GATA6 as the marker of classical versus basal-like pancreatic cancer, Ontario Institute for Cancer Research, Princess Margaret Cancer Centre.
Shares COMPASS: real-time sequencing of advanced pancreatic cancer for treatment selection, GATA6 as the marker of classical versus basal-like pancreatic cancer, KRAS allelic imbalance and mutant KRAS dosage in pancreatic cancer, KRAS.
Shares Ontario Institute for Cancer Research, Princess Margaret Cancer Centre, Single-cell & spatial profiling.
Shares Nature Genetics, Clonal evolution & minimal residual disease, Whole-exome & whole-genome sequencing, Pancreatic ductal adenocarcinoma.
Shares David A. Tuveson, Cold Spring Harbor Laboratory, Single-cell & spatial profiling, Pancreatic ductal adenocarcinoma.
Shares Ontario Institute for Cancer Research, Princess Margaret Cancer Centre, Single-cell & spatial profiling, Pancreatic ductal adenocarcinoma.