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Esco2 deficiencies accelerate tumor onset in a LOH-sensitive background.(A) Zebrafish Kaplan-Meier curves for tumor-free survival for wild-type, esco22865/+, p53J19/+, esco22865/+; p53J19/+, p53J19/J19, and esco22865/+; p53J19/J19 cohorts. Compared cohorts were established by natural single pair breeding of esco2m/+ x AB (wild-type strain), esco2m/+; p53m/m x AB, or esco2m/+; p53m/m x p53m/m parents (all cohorts were n = 96). The p-value = <0.0001 when comparing p53J19/+ with esco22865/+; p53J19/+ cohorts based on Log-rank (Mantel-Cox) test. (B) Mouse Kaplan-Meier curves for tumor-free survival for wild-type, Esco2 +/-, p53 +/-, Esco2 +/-; p53 +/- and p53 -/- cohorts (cohorts with p53+/+ and p53+/- background were n>60 and cohorts with p53-/- background were n>6). The p-value = <0.05 when comparing p53+/- with esco2+/-; p53+/- curves based on Log-rank (Mantel-Cox) test. (C) Frequency of p53 wild-type loss of heterozygosity (LOH) and esco2 wild-type LOH in zebrafish tumors; as well as the frequency of tumors being Malignant Peripheral Nerve sheath tumors (MPNST). (D) Pie charts showing tumor spectrum in Esco2+/+; p53+/- (left panel) and Esco2+/-; p53+/- (right panel) mice. No statistically significant in tumor spectrum with Chi-square test. (E) Percentage of patients with LOH on TP53 in TCGA cancer samples with or w/o ESCO2 mutation/deletion. The number of WT and deficient samples in each tumor were indicated. BLCA: 393 WT + 13 Deficient; BRCA: 935 WT + 29 Deficient; COADREAD: 482 WT + 38 Deficient; LIHC: 333 WT + 21 Deficient; LUND: 495 WT + 10 Deficient; LUSC: 478 WT + 8 Deficient; OV: 383 WT + 46 Deficient; PRAD: 481 WT + 6 Deficient; UCEC: 479 WT + 43 Deficient. * indicates p<0.05 from Fisher’s exact test. (F) Percentage of patients with LOH covering in tumor suppressor gene PTEN, BRCA1, BRCA2, RB1, NF1 and APC in the TCGA dataset. N = 4,126 for ESCO2-WT cohort and N = 193 for ESCO2-deficiency cohort. ** and *** indicate p<0.01 and p<0.001 with Fisher’s Exact test. (G) The number of LOH events per tumor sample in TCGA cancer samples with or w/o ESCO2 mutation/deletion. The number of WT and deficient samples in each tumor were indicated: PRAD: 481 WT + 6 Deficient; UCEC: 479 WT + 43 Deficient; OV: 383 WT + 46 Deficient; LUAD: 495 WT + 10 Deficient; COADREAD: 482 WT + 38 Deficient; LUSC: 478 WT + 8 Deficient; BRCA: 935 WT + 29 Deficient; BLCA: 393 WT + 13 Deficient. * and ** indicate p<0.05 and p<0.01 from Mann-Whitney test.
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