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Oral squamous cell carcinoma is a prominent cancer worldwide, particularly in Taiwan. By integrating omics analyses in 50 matched samples, we uncover in Taiwanese patients a predominant mutation signature associated with cytidine deaminase APOBEC, which correlates with the upregulation of  APOBEC3A  expression in the  APOBEC3  gene cluster at 22q13.  APOBEC3A  expression is significantly higher in tumors carrying  APOBEC3B- deletion allele(s). High-level  APOBEC3A  expression is associated with better overall survival, especially among patients carrying  APOBEC3B -deletion alleles, as examined in a second cohort ( n  = 188;  p  = 0.004). The frequency of  APOBEC3B -deletion alleles is ~50% in 143 genotyped oral squamous cell carcinoma -Taiwan samples (27 A3B   −/− :89 A3B   +/− :27 A3B   +/+ ), compared to the 5.8% found in 314 OSCC-TCGA samples. We thus report a frequent APOBEC mutational profile, which relates to a  APOBEC3B -deletion germline polymorphism in Taiwanese oral squamous cell carcinoma that impacts expression of  APOBEC3A , and is shown to be of clinical prognostic relevance. Our finding might be recapitulated by genomic studies in other cancer types.

APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism