Fig. 2

CRISPR and transposon mutagenesis screens enable cancer gene identification in vivo. Left: a typical pooled, sgRNA CRISPR library is transduced into Cas9-knockin mice, leading to the loss of a TSG in each cell, driving oncogenesis. Multiplexed delivery of sgRNA constructs can alternatively be achieved leading to simultaneous editing of multiple TSGs (not represented). Right: mice harboring transposons and transposase develop spontaneous tumors due to transposon-induced activating and inactivating mutations. Both oncogenes and TSGs can be identified by deep sequencing of transposon hits at different stages of tumor progression, revealing genetic routes of cancer evolution. Symbol notation: cross = inactivating mutation; bent arrow = activating mutation; different colors denote mutations in different cancer genes