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Nat Commun. 2019 Aug 8;10(1):3574. doi: 10.1038/s41467-019-11415-2.

Comprehensive transcriptomic analysis of cell lines as models of primary tumors across 22 tumor types.

Author information

1
Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, 94158, CA, USA.
2
Department of Pediatrics, University of California, San Francisco, San Francisco, 94143, CA, USA.
3
Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, 49503, MI, USA.
4
Department of Pharmacology and Toxicology, College of Human Medicine, Michigan State University, Grand Rapids, 49503, MI, USA.
5
Department of Genetics, Stanford University, Stanford, 94305, CA, USA.
6
Buck Institute for Research on Aging, Novato, 94945, CA, USA.
7
Department of Surgery, University of California, San Francisco, San Francisco, 94143, CA, USA.
8
Department of Laboratory Medicine, University of California, San Francisco, San Francisco, 94143, CA, USA.
9
Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, 94158, CA, USA. Marina.Sirota@ucsf.edu.
10
Department of Pediatrics, University of California, San Francisco, San Francisco, 94143, CA, USA. Marina.Sirota@ucsf.edu.

Abstract

Cancer cell lines are a cornerstone of cancer research but previous studies have shown that not all cell lines are equal in their ability to model primary tumors. Here we present a comprehensive pan-cancer analysis utilizing transcriptomic profiles from The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia to evaluate cell lines as models of primary tumors across 22 tumor types. We perform correlation analysis and gene set enrichment analysis to understand the differences between cell lines and primary tumors. Additionally, we classify cell lines into tumor subtypes in 9 tumor types. We present our pancreatic cancer results as a case study and find that the commonly used cell line MIA PaCa-2 is transcriptionally unrepresentative of primary pancreatic adenocarcinomas. Lastly, we propose a new cell line panel, the TCGA-110-CL, for pan-cancer studies. This study provides a resource to help researchers select more representative cell line models.

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