Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution
Top Cited Papers
- 13 January 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 52 (2), 231-240
- https://doi.org/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.This publication has 50 references indexed in Scilit:
- Pan-cancer patterns of somatic copy number alterationNature Genetics, 2013
- Pancreatic cancer genomes reveal aberrations in axon guidance pathway genesNature, 2012
- DELLY: structural variant discovery by integrated paired-end and split-read analysisBioinformatics, 2012
- Strelka: accurate somatic small-variant calling from sequenced tumor–normal sample pairsBioinformatics, 2012
- CREST maps somatic structural variation in cancer genomes with base-pair resolutionNature Methods, 2011
- The patterns and dynamics of genomic instability in metastatic pancreatic cancerNature, 2010
- ConsensusClusterPlus: a class discovery tool with confidence assessments and item trackingBioinformatics, 2010
- A Gene Expression Signature Associated with “K-Ras Addiction” Reveals Regulators of EMT and Tumor Cell SurvivalCancer Cell, 2009
- Fast and accurate short read alignment with Burrows–Wheeler transformBioinformatics, 2009
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005