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APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism.
Chen TW, Lee CC, Liu H, Wu CS, Pickering CR, Huang PJ, Wang J,
Chang IY, Yeh YM, Chen CD, Li HP, Luo JD, Tan BC, Chan TEH,
Hsueh C, Chu LJ, Chen YT, Zhang B, Yang CY, Wu CC, Hsu CW, See
LC, Tang P, Yu JS, Liao WC, Chiang WF, Rodriguez H, Myers J, Chang
KP, Chag YS. APOBEC3A is an oral cancer prognostic biomarker in
Taiwanese carriers of an APOBEC deletion polymorphism.
Nat Commun. 2017. 8(1):465.

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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