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Mapping the in vivo fitness landscape of lung adenocarcinoma tumor suppression in mice

Nat Genet. 2018-04-01; 
Zoë N Rogers, Christopher D McFarland, Ian P Winters, Jose A Seoane, Jennifer J Brady, Stephanie Yoon, Christina Curtis, Dmitri A Petrov, Monte M Winslow
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Mutant Libraries … ORF over-expression. Open reading frames (ORFs) of wild-type MEK1 and mutants thereof were synthesized (Genscript) and cloned into the lentiviral vector pLX_304 (Addgene 25890)16. For each construct, virus was prepared as described above … Get A Quote

摘要

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.

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