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

Ting Wen Chen, Chi Ching Lee, Hsuan Liu, Chi Sheng Wu, Curtis R. Pickering, Po Jung Huang, Jing Wang, Ian Yi Feng Chang, Yuan Ming Yeh, Chih De Chen, Hsin Pai Li, Ji Dung Luo, Bertrand Chin Ming Tan, Timothy En Haw Chan, Chuen Hsueh, Lichieh Julie Chu, Yi Ting Chen, Bing Zhang, Chia Yu Yang, Chih Ching WuChia Wei Hsu, Lai Chu See, Petrus Tang, Jau Song Yu, Wei Chao Liao, Wei Fan Chiang, Henry Rodriguez, Jeffrey N. Myers, Kai Ping Chang, Yu Sun Chang

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46 Scopus citations

Abstract

© 2017 The Author(s). 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.
Original languageAmerican English
Article number465
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - 6 Sep 2017

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