Genetic interactions with STAG2 include modification of overall tumor suppression and functional dependency with PAXIP1 and PAGR1. (a) List of candidate gene criteria for a pool of 468 barcoded Lenti-sgRNA/Cre vectors. (b) Tumor initiation with Lenti-U6^BC-sgRNA/Cre vectors in KT;H11^LSL-Cas9, KT;^H11LSL-Cas9;Stag2^flox, and KT mice. Number of mice in each group is indicated. Sequencing was performed on each tumor-bearing lung 14 wk after tumor initiation, followed by analysis to quantify tumorigenesis. (c) Bar plot with percent of genes in each candidate category with differential effects between KT;H11^LSL-Cas9 and KT;H11^LSL-Cas9;Stag2^flox. (d) Relative mean tumor size of tumors with sgRNAs targeting Stag2 (normalized to sgInert) in KT;H11^LSL-Cas9 mice compared to KT;H11^LSL-Cas9;Stag2^flox mice. Mean ± 95% confidence intervals are shown. (e) Relative mean tumor size of tumors with sgRNAs targeting Setd2, Stk11, or Tsc1 (normalized to sgInert) in KT;H11^LSL-Cas9 mice compared with KT;H11^LSL-Cas9;Stag2^flox mice. Mean ± 95% confidence intervals are shown. (f) Relative mean tumor size of tumors with sgRNAs targeting Paxip1 or Pagr1 (normalized to sgInert) in KT;H11^LSL-Cas9 mice compared with KT;H11^LSL-Cas9;Stag2^flox mice. Mean ± 95% confidence intervals are shown. (g) Comparison of average relative tumor number for sgRNAs targeting Stag1, Stag2, Pole2 (essential gene), or Inerts in KT;H11^LSL-Cas9 mice and KT;H11^LSL-Cas9;Stag2^flox mice. Mean ± 95% confidence intervals are shown. Raw values and significance of each effect are shown in Table S4. Data for KT;H11^LSL-Cas9 and KT mice represent one replicate of two independent experiments.