Second-hit driver alterations revealed by WES in CRISPR screening. (A) Landscape of significantly recurrent second-hit somatic alterations in the entire cohort. Disease type, involved organ, and CRISPR library pool (bottom) as well as q values (right) are shown. Significantly recurrent genes (q < 1 × 10⁻¹⁰) are marked with asterisks. (B) Number of samples harboring second-hit alterations for each gene in the entire cohort (n = 104). (C) Type and position of Trp53 second-hit alterations in the entire cohort. (D) Proportion of copy number–altered segments in samples with and without Trp53 alterations in B-cell lymphoma (n = 19) and T-ALL/LBL (n = 15). Brunner-Munzel test. (E) Stat5a/Stat5b amplification in a B-cell lymphoma case (SCR208). (F) Nup214::Abl1 fusion in a B-ALL/LBL case (SCR009). aa, amino acids; AUL, acute undifferentiated leukemia; ITD, internal tandem dupulication; NES, nuclear export signal; NLS, nuclear localization signal; SNV, single-nucleotide variant; SV, structural variation.