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


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.

SUBMITTER: Rogers ZN 

PROVIDER: S-EPMC6061949 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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

Rogers Zoë N ZN   McFarland Christopher D CD   Winters Ian P IP   Seoane Jose A JA   Brady Jennifer J JJ   Yoon Stephanie S   Curtis Christina C   Petrov Dmitri A DA   Winslow Monte M MM  

Nature genetics 20180402 4


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 effec  ...[more]

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