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)
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 |
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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 CSHL Cancer Center Program > Cellular Communication in Cancer Program |
Depositing User: | Adrian Gomez |
Date: | 13 January 2020 |
Date Deposited: | 15 Jan 2020 21:00 |
Last Modified: | 26 Oct 2020 15:37 |
Related URLs: | |
Dataset ID: |
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URI: | https://repository.cshl.edu/id/eprint/38908 |
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