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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution
Nature Genetics, Volume 52, No. 2, Year 2020
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Description
Pancreatic adenocarcinoma presents as a spectrum of a highly aggressive disease in patients. The basis of this disease heterogeneity has proved difficult to resolve due to poor tumor cellularity and extensive genomic instability. To address this, a dataset of whole genomes and transcriptomes was generated from purified epithelium of primary and metastatic tumors. Transcriptome analysis demonstrated that molecular subtypes are a product of a gene expression continuum driven by a mixture of intratumoral subpopulations, which was confirmed by single-cell analysis. Integrated whole-genome analysis uncovered that molecular subtypes are linked to specific copy number aberrations in genes such as mutant KRAS and GATA6. By mapping tumor genetic histories, tetraploidization emerged as a key mutational process behind these events. Taken together, these data support the premise that the constellation of genomic aberrations in the tumor gives rise to the molecular subtype, and that disease heterogeneity is due to ongoing genomic instability during progression. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
Authors & Co-Authors
Chan-Seng-Yue, Michelle A.
Canada, Toronto
Princess Margaret Cancer Centre
Canada, Toronto
Ontario Institute for Cancer Research
Bartlett, John M.S.
Canada, Toronto
Ontario Institute for Cancer Research
Schaeffer, David F.
Canada, Vancouver
Vancouver General Hospital
Jones, Steven J.M.
Canada, Vancouver
Canada‘s Michael Smith Genome Sciences Centre
Canada, Vancouver
The University of British Columbia
Marra, Marco A.
Canada, Vancouver
Canada‘s Michael Smith Genome Sciences Centre
Canada, Vancouver
The University of British Columbia
Chetty, Runjan M.
Canada, Toronto
University Health Network University of Toronto
Zogopoulos, George
Canada, Montreal
L'institut de Recherche du Centre Universitaire de Santé Mcgill
Canada, Montreal
Université Mcgill
Haibe-Kains, Benjamin
Canada, Toronto
Princess Margaret Cancer Centre
Canada, Toronto
Ontario Institute for Cancer Research
Canada, Toronto
University of Toronto
Campbell, Peter J.
United Kingdom, Hinxton
Wellcome Sanger Institute
United Kingdom, Cambridge
University of Cambridge
Knox, Jennifer J.
Canada, Toronto
Ontario Institute for Cancer Research
Canada, Toronto
University Health Network University of Toronto
Fischer, Sandra E.
Canada, Toronto
University Health Network University of Toronto
Canada, Toronto
University of Toronto
Gallinger, Steven J.
Canada, Toronto
Ontario Institute for Cancer Research
Canada, Toronto
University Health Network University of Toronto
Canada, Toronto
Mount Sinai Hospital of University of Toronto
Canada, Toronto
University of Toronto
Statistics
Citations: 281
Authors: 12
Affiliations: 16
Identifiers
Doi:
10.1038/s41588-019-0566-9
ISSN:
10614036
Research Areas
Cancer
Genetics And Genomics