Genomic Correlates of APOBEC-Associated Mutagenesis in Esophageal Squamous Cell Carcinoma

APOBEC-associated mutagenesis in 552 esophageal squamous cell carcinoma tumors shows a strong inverse link with SBS18, with Pearson r = -0.319 (P = 1.59 x 10^-14) in absolute counts.

• Why it matters: APOBEC-driven mutagenesis varies widely between ESCC tumors, but the genomic features explaining that intertumoral variability are not fully defined. Accounting for how mutational signatures are represented could clarify which signals are robust.
• What they did: The study analyzed mutational signatures in 552 ESCC tumors from eight countries, quantifying APOBEC burden as SBS2 plus SBS13 using absolute mutation counts and proportional contributions. It tested correlations with other signatures, total SBS burden, driver alterations, and country using correlation, sensitivity, and multivariable models.
• The result: SBS18 remained inversely associated across multiple comparison types (e.g., Spearman rho = -0.527 for proportion vs proportion), while several other signatures depended on whether proportions or absolute counts were used. The multivariable model fit in-sample (R^2 = 0.400) but cross-validated performance was lower and variable (mean R^2 = 0.273), and country added little (delta R^2 = 0.008).

AI summary of the abstract · may contain errors · not medical advice · read the paper.