Nat Commun. 2017 Sep 6;8(1):465.
Chen TW1,2, Lee CC1,2,3, Liu H1,4,5,6, Wu CS1,7, Pickering CR8, Huang PJ1,2,9,10, Wang J11, Chang IY1,2, Yeh YM1,2, Chen CD1, Li HP1,4,12,13, Luo JD1,2, Tan BC1,4,9,14, Chan TEH4, Hsueh C15,16, Chu LJ1,17, Chen YT1,4,9, Zhang B18, Yang CY1,6,12, Wu CC1,7,19, Hsu CW1, See LC20,21, Tang P1,2,22,23, Yu JS1,17,24, Liao WC1,7, Chiang WF25,26, Rodriguez H27, Myers JN7, Chang KP28,29, Chang YS30,31,32.
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 (27A3B -/-:89A3B +/-:27A3B +/+), 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.Oral squamous cell carcinoma is a prevalent malignancy in Taiwan. Here, the authors show that OSCC in Taiwanese show a frequent deletion polymorphism in the cytidine deaminases gene cluster APOBEC3 resulting in increased expression of A3A, which is shown to be of clinical prognostic relevance.