Fig. 2: APOBEC3B expression correlates with multiple measures of CIN, and APOBEC mutagenesis is subclonally enriched in TN EGFRmut patients from the TRACERx421 (Tx421) dataset.
From: The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance
a, Correlation between APOBEC3B (A3B) expression and percent missegregation errors calculated using patients with EGFRmut lung adenocarcinoma (n = 13 tumors; Spearman, R = 0.59; P = 0.038). b, Significant correlation between A3B expression and CIN70 GSEA score calculated using EGFRmut tumors from patients with lung adenocarcinoma (n = 19 tumors; Spearman, R = 0.59; P = 0.009). c, Significant correlation between A3B expression and CIN70 GSEA score calculated using EGFRmut tumor regions in patients with lung adenocarcinoma (n = 42 tumor regions; Spearman, R = 0.64; P < 9 × 10−6). d, Correlation between A3B expression and subclonal CIN fraction calculated in EGFRmut patients with lung adenocarcinoma (n = 19 tumors; bootstrapped Spearman, R = 0.5; P = 0.032). e, Significant correlation between percent missegregation errors (anaphase bridges (bridges) and lagging chromosomes (lagging)) and CIN70 score calculated using tumors from patients (n = 112 tumors; Spearman, R = 0.27; P = 0.0038). f, Significant correlation between A3B expression and CIN70 GSEA score calculated using tumors from patients with lung adenocarcinoma (n = 188 tumors; Spearman, R = 0.56; P < 2 × 10−16). g, Significant correlation between A3B expression and CIN70 GSEA score calculated using tumor regions in patients with lung adenocarcinoma (n = 466 tumor regions; Spearman, R = 0.54; P < 2 × 10−16). h, Correlation between A3B expression and subclonal CIN fraction calculated patients with lung adenocarcinoma in the Tx421 cohort (n = 168 tumors; bootstrapped Spearman, R = 0.26; P = 0.00087). i, Comparisons between C>T and C>G mutation counts at TCN and TCW trinucleotide context and percentage of genome altered subclonally (n = 25, two-sided Pearson, TCW R = 0.49, P = 0.015; TCN R = 0.52, P = 0.0092). j, Comparison of clonal and subclonal APOBEC-associated mutation signature (clonal APOBEC–subclonal APOBEC) in patients with EGFR driver mutations (1, 1a, exon 19 deletion). White bars indicate that the patient is TP53 WT or has a subclonal TP53 mutation. Red bars indicate that the patient has a clonal TP53 mutation (n = 23, one-sided Wilcoxon, P = 1 × 10−4). k, Number of APOBEC-associated mutations in patients with EGFR driver mutations (1, 1a, exon 19 deletion). Colors indicate clonal or subclonal APOBEC or non-APOBEC-associated mutations (n = 23). All analyses were performed on samples from the Tx421 cohort. GSEA, gene set enrichment analysis; NES, normalized enrichment score; TMM, trimmed mean of M values.
