Figure S1.
The effect of STAG2 inactivation is highly correlated with that of PAXIP1 and PAGR1 inactivation in human cancer cell lines, and genetic interactions with STAG2 are robust to different measures of tumorigenesis and tumor growth in oncogenic Kras lung cancer in vivo. (a and b) Gene knockout effects for PAXIP1 and STAG2 inactivation (a) and for PAGR1 and STAG2 inactivation (b). Each dot represents a cell line. Cell lines with STAG2 mutation were excluded. Spearman’s r and Pearson rho are indicated. (c) Bell curve showing the frequency of Spearman’s correlations across all pairwise comparisons in DepMap. STAG2-PAGR1 and STAG2-PAXIP1 correlations are indicated. (d and e) Genes with the highest Spearman’s correlation with the effect of STAG2 inactivation from DepMap. Data from cell lines with oncogenic mutations at codons 12 or 13 of KRAS (d) and lung adenocarcinoma cell lines with oncogenic mutations at codons 12 or 13 of KRAS (e). Cell lines with STAG2 mutation were excluded. PAXIP1 and PAGR1 are colored bars. Core cohesin complex genes are white bars. (f and g) Gene effects for PAXIP1 and STAG2 inactivation (f) and for PAGR1 and STAG2 inactivation (g) in AML. Each dot represents a cell line. Cell lines with STAG2 mutations were excluded. Spearman’s r and Pearson rho are indicated. (h and i) Tables indicating Spearman’s r and Pearson rho for PAXIP1 gene effect (h) and for PAGR1 gene effect (i) in bladder cancer and Ewing’s sarcoma. Cell lines with STAG2 mutations were excluded. (j) Relative tumor number (normalized to KT and sgInert). Mean ± 95% confidence intervals are shown. Dotted line indicates no effect. Raw values and significance of each effect are shown in Table S2 (j). (k) Western blot on sorted neoplastic cells from KT;H11LSL-Cas9 mice with tumors initiated with the indicated Lenti-sgRNA/Cre vectors. Data represents one replicate of three independent experiments. (l) Tumor sizes at the indicated percentiles for tumors with sgRNA targeting Setd2, Stk11, or Tsc1 (normalized to sgInert) in KT;H11LSL-Cas9 and KT;H11LSL-Cas9;Stag2flox mice. Each gene was targeted with three sgRNAs. Error bars indicate 95% confidence intervals. Dotted line indicates no effect. (m) Tumor sizes at the indicated percentiles for tumors with sgRNA targeting Paxip1 or Pagr1 (normalized to sgInert) in KT;H11LSL-Cas9 and KT;H11LSL-Cas9;Stag2flox mice. Each gene was targeted with three and six sgRNAs, respectively. Error bars indicate 95% confidence intervals. Dotted line indicates no effect. (n) Comparison of relative tumor number for tumors with sgRNAs targeting for Stag1, Stag2, or Pole2 in KT;H11LSL-Cas9 mice compared to KT;H11LSL-Cas9;Stag2flox mice. Mean ± 95% confidence intervals are shown. Raw values and significance of each effect are shown in Table S4 (l–n). Source data are available for this figure: SourceData FS1.

The effect of STAG2 inactivation is highly correlated with that of PAXIP1 and PAGR1 inactivation in human cancer cell lines, and genetic interactions with STAG2 are robust to different measures of tumorigenesis and tumor growth in oncogenic Kras lung cancer in vivo. (a and b) Gene knockout effects for PAXIP1 and STAG2 inactivation (a) and for PAGR1 and STAG2 inactivation (b). Each dot represents a cell line. Cell lines with STAG2 mutation were excluded. Spearman’s r and Pearson rho are indicated. (c) Bell curve showing the frequency of Spearman’s correlations across all pairwise comparisons in DepMap. STAG2-PAGR1 and STAG2-PAXIP1 correlations are indicated. (d and e) Genes with the highest Spearman’s correlation with the effect of STAG2 inactivation from DepMap. Data from cell lines with oncogenic mutations at codons 12 or 13 of KRAS (d) and lung adenocarcinoma cell lines with oncogenic mutations at codons 12 or 13 of KRAS (e). Cell lines with STAG2 mutation were excluded. PAXIP1 and PAGR1 are colored bars. Core cohesin complex genes are white bars. (f and g) Gene effects for PAXIP1 and STAG2 inactivation (f) and for PAGR1 and STAG2 inactivation (g) in AML. Each dot represents a cell line. Cell lines with STAG2 mutations were excluded. Spearman’s r and Pearson rho are indicated. (h and i) Tables indicating Spearman’s r and Pearson rho for PAXIP1 gene effect (h) and for PAGR1 gene effect (i) in bladder cancer and Ewing’s sarcoma. Cell lines with STAG2 mutations were excluded. (j) Relative tumor number (normalized to KT and sgInert). Mean ± 95% confidence intervals are shown. Dotted line indicates no effect. Raw values and significance of each effect are shown in Table S2 (j). (k) Western blot on sorted neoplastic cells from KT;H11LSL-Cas9 mice with tumors initiated with the indicated Lenti-sgRNA/Cre vectors. Data represents one replicate of three independent experiments. (l) Tumor sizes at the indicated percentiles for tumors with sgRNA targeting Setd2, Stk11, or Tsc1 (normalized to sgInert) in KT;H11LSL-Cas9 and KT;H11LSL-Cas9;Stag2flox mice. Each gene was targeted with three sgRNAs. Error bars indicate 95% confidence intervals. Dotted line indicates no effect. (m) Tumor sizes at the indicated percentiles for tumors with sgRNA targeting Paxip1 or Pagr1 (normalized to sgInert) in KT;H11LSL-Cas9 and KT;H11LSL-Cas9;Stag2flox mice. Each gene was targeted with three and six sgRNAs, respectively. Error bars indicate 95% confidence intervals. Dotted line indicates no effect. (n) Comparison of relative tumor number for tumors with sgRNAs targeting for Stag1, Stag2, or Pole2 in KT;H11LSL-Cas9 mice compared to KT;H11LSL-Cas9;Stag2flox mice. Mean ± 95% confidence intervals are shown. Raw values and significance of each effect are shown in Table S4 (l–n). Source data are available for this figure: SourceData FS1.

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