Abstract

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.

Details

Title
APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism
Author
Ting-Wen, Chen 1 ; Chi-Ching, Lee 2 ; Liu, Hsuan 3 ; Chi-Sheng, Wu 4 ; Pickering, Curtis R 5 ; Po-Jung, Huang 6 ; Wang, Jing 7 ; Ian Yi-Feng Chang 1 ; Yuan-Ming Yeh 1 ; Chih-De, Chen 8 ; Hsin-Pai, Li 9 ; Ji-Dung Luo 1 ; Tan, Bertrand Chin-Ming 10 ; Timothy En Haw Chan 11   VIAFID ORCID Logo  ; Hsueh, Chuen 12 ; Lichieh, Julie Chu 13 ; Yi-Ting, Chen 14   VIAFID ORCID Logo  ; Zhang, Bing 15   VIAFID ORCID Logo  ; Chia-Yu, Yang 16 ; Chih-Ching Wu 17 ; Chia-Wei, Hsu 8 ; Lai-Chu, See 18 ; Tang, Petrus 19 ; Jau-Song, Yu 20 ; Wei-Chao, Liao 4 ; Wei-Fan, Chiang 21 ; Rodriguez, Henry 22 ; Myers, Jeffrey N 23 ; Kai-Ping, Chang 24   VIAFID ORCID Logo  ; Yu-Sun, Chang 25 

1  Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan; Bioinformatics Center, Chang Gung University, Guishan, Taoyuan, Taiwan 
2  Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan; Bioinformatics Center, Chang Gung University, Guishan, Taoyuan, Taiwan; Department and Graduate Institute of Computer Science and Information Engineering, Chang Gung University, Guishan, Taoyuan, Taiwan 
3  Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, Chang Gung University, Guishan, Taoyuan, Taiwan; Department of Biochemistry, Chang Gung University, Guishan, Taoyuan, Taiwan; Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Linkou, Gueishan, Taoyuan, Taiwan 
4  Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan; Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital at Linkou, Gueishan, Taoyuan, Taiwan 
5  Departments of Head and Neck Surgery, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA 
6  Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan; Bioinformatics Center, Chang Gung University, Guishan, Taoyuan, Taiwan; Department of Biomedical Sciences, Chang Gung University, Guishan, Taoyuan, Taiwan; Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital at Linkou, Gueishan, Taoyuan, Taiwan 
7  Departments of Biostatistics, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA 
8  Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan 
9  Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, Chang Gung University, Guishan, Taoyuan, Taiwan; Department of Microbiology and Immunology, Chang Gung University, Guishan, Taoyuan, Taiwan; Division of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Gueishan, Taoyuan, Taiwan 
10  Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, Chang Gung University, Guishan, Taoyuan, Taiwan; Department of Biomedical Sciences, Chang Gung University, Guishan, Taoyuan, Taiwan; Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou, Gueishan, Taoyuan, Taiwan 
11  Graduate Institute of Biomedical Sciences, Chang Gung University, Guishan, Taoyuan, Taiwan 
12  Pathology Core of the Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan; Department of Pathology, Chang Gung Memorial Hospital at Linkou, Gueishan, Taoyuan, Taiwan 
13  Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan; Liver Research Center, Chang Gung Memorial Hospital at Linkou, Gueishan, Taoyuan, Taiwan 
14  Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, Chang Gung University, Guishan, Taoyuan, Taiwan; Department of Biomedical Sciences, Chang Gung University, Guishan, Taoyuan, Taiwan 
15  Department of Molecular and Human Genetics Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas, USA 
16  Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan; Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Linkou, Gueishan, Taoyuan, Taiwan; Department of Microbiology and Immunology, Chang Gung University, Guishan, Taoyuan, Taiwan 
17  Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan; Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital at Linkou, Gueishan, Taoyuan, Taiwan; Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Guishan, Taoyuan, Taiwan 
18  Department of Public Health, Chang Gung University, Guishan, Taoyuan, Taiwan; Biostatistics Core Laboratory, Chang Gung University, Guishan, Taoyuan, Taiwan 
19  Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan; Bioinformatics Center, Chang Gung University, Guishan, Taoyuan, Taiwan; Molecular Regulation and Bioinformatics Laboratory, Chang Gung University, Guishan, Taoyuan, Taiwan; Molecular Infectious Diseases Research Center, Chang Gung Memorial Hospital at Linkou, Gueishan, Taoyuan, Taiwan 
20  Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan; Liver Research Center, Chang Gung Memorial Hospital at Linkou, Gueishan, Taoyuan, Taiwan; Department of Cell and Molecular Biology, Chang Gung University, Guishan, Taoyuan, Taiwan 
21  Department of Oral & Maxillofacial Surgery, Chi-Mei Medical Center, Liouying, Taiwan; School of Dentistry, National Yang Ming University, Taipei, Taiwan 
22  Office of Cancer Clinical Proteomics Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA 
23  Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital at Linkou, Gueishan, Taoyuan, Taiwan 
24  Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital at Linkou, Gueishan, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Guishan, Taoyuan, Taiwan 
25  Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, Chang Gung University, Guishan, Taoyuan, Taiwan; Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital at Linkou, Gueishan, Taoyuan, Taiwan 
Pages
1-13
Publication year
2017
Publication date
Sep 2017
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-017-00493-9
ProQuest document ID
1936203394
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.