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

Chan-Seng-Yue, M., Kim, J. C., Wilson, G. W., Ng, K., Figueroa, E. F., O'Kane, G. M., Connor, A. A., Denroche, R. E., Grant, R. C., McLeod, J., Wilson, J. M., Jang, G. H., Zhang, A., Liang, S. B., Borgida, A., Chadwick, D., Kalimuthu, S., Lungu, I., Bartlett, J. M. S., Krzyzanowski, P. M., Sandhu, V., Tiriac, H., Froeling, F. E. M., Karasinska, J. M., Topham, J. T., Renouf, D. J., Schaeffer, D. F., Jones, S. J. M., Marra, M. A., Laskin, J., Chetty, R., Stein, L. D., Zogopoulos, G., Haibe-Kains, B., Campbell, P. J., Tuveson, D. A., Knox, J. J., Fischer, S. E., Gallinger, S., Notta, F. (January 2020) Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution. Nat Genet. ISSN 1061-4036 (Public Dataset)

URL: https://www.ncbi.nlm.nih.gov/pubmed/31932696
DOI: 10.1038/s41588-019-0566-9

Abstract

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.

Item Type: Paper
Additional Information: Author Correction: An amendment to this paper has been published and can be accessed via a link: https://www.nature.com/articles/s41588-020-0588-3.
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
organism description > animal > mammal > rodent > mouse
diseases & disorders > cancer > cancer types > pancreatic cancer
Investigative techniques and equipment > assays > Single cell sequencing
CSHL Authors:
Communities: CSHL labs > Tuveson lab
Depositing User: Adrian Gomez
Date: 13 January 2020
Date Deposited: 15 Jan 2020 21:00
Last Modified: 18 Feb 2020 15:38
Related URLs:
Dataset ID:
  • Raw data are freely available from EGA under accession code EGAS00001002543.
URI: https://repository.cshl.edu/id/eprint/38908

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving