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

Nat Commun. 2017 Sep 6;8(1):465.
doi: 10.1038/s41467-017-00493-9.

Chen TW1,2Lee CC1,2,3Liu H1,4,5,6Wu CS1,7Pickering CR8Huang PJ1,2,9,10Wang J11Chang IY1,2Yeh YM1,2Chen CD1Li HP1,4,12,13Luo JD1,2Tan BC1,4,9,14Chan TEH4Hsueh C15,16Chu LJ1,17Chen YT1,4,9Zhang B18Yang CY1,6,12Wu CC1,7,19Hsu CW1See LC20,21Tang P1,2,22,23Yu JS1,17,24Liao WC1,7Chiang WF25,26Rodriguez H27Myers JN7Chang KP28,29Chang 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.




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