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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.
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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