1. Mapping the in vivo fitness landscape of lung adenocarcinoma tumor suppression in mice
- Author
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Jose A. Seoane, Jennifer J. Brady, Ian P. Winters, Christina Curtis, Stephanie Yoon, Monte M. Winslow, Zoë N. Rogers, Dmitri A. Petrov, and Christopher D. McFarland
- Subjects
0301 basic medicine ,Lung Neoplasms ,Transgene ,Adenocarcinoma of Lung ,Mice, Transgenic ,Context (language use) ,Biology ,Retinoblastoma Protein ,Article ,Mice ,03 medical and health sciences ,Genome editing ,Genetics ,medicine ,Animals ,DNA Barcoding, Taxonomic ,Humans ,CRISPR ,Genes, Tumor Suppressor ,Genes, Suppressor ,Gene ,Gene Editing ,High-Throughput Nucleotide Sequencing ,Cancer ,Sequence Analysis, DNA ,Genes, p53 ,medicine.disease ,030104 developmental biology ,Cancer research ,Adenocarcinoma ,Genetic Fitness ,CRISPR-Cas Systems ,Functional genomics ,Gene Deletion - Abstract
The functional impact of most genomic alterations found in cancer, alone or in combination, remains largely unknown. Here we integrate tumor barcoding, CRISPR/Cas9-mediated genome editing and ultra-deep barcode sequencing to interrogate pairwise combinations of tumor suppressor alterations in autochthonous mouse models of human lung adenocarcinoma. We map the tumor suppressive effects of 31 common lung adenocarcinoma genotypes and identify a landscape of context dependence and differential effect strengths.
- Published
- 2018