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 Wu; Chia 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

doi:10.1038/s41467-017-00493-9

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

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

90 Scopus citations

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.

Original language	English
Article number	465
Journal	Nature Communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-00493-9
State	Published - 01 12 2017

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Publisher Copyright:
© 2017 The Author(s).

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Chen, T. W., Lee, C. C., Liu, H., Wu, C. S., Pickering, C. R., Huang, P. J., Wang, J., Chang, I. Y. F., Yeh, Y. M., Chen, C. D., Li, H. P., Luo, J. D., Tan, B. C. M., Chan, T. E. H., Hsueh, C., Chu, L. J., Chen, Y. T., Zhang, B., Yang, C. Y., ... Chang, Y. S. (2017). APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism. Nature Communications, 8(1), Article 465. https://doi.org/10.1038/s41467-017-00493-9

@article{52af04d043984a0d964293a766e49785,

title = "APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = dec,

day = "1",

doi = "10.1038/s41467-017-00493-9",

language = "英语",

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Chen, TW, Lee, CC , Liu, H , Wu, CS, Pickering, CR, Huang, PJ, Wang, J, Chang, IYF, Yeh, YM, Chen, CD, Li, HP, Luo, JD, Tan, BCM, 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, JN, Chang, KP & Chang, YS 2017, 'APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism', Nature Communications, vol. 8, no. 1, 465. https://doi.org/10.1038/s41467-017-00493-9

TY - JOUR

T1 - APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism

AU - Chen, Ting Wen

AU - Lee, Chi Ching

AU - Liu, Hsuan

AU - Wu, Chi Sheng

AU - Pickering, Curtis R.

AU - Huang, Po Jung

AU - Wang, Jing

AU - Chang, Ian Yi Feng

AU - Yeh, Yuan Ming

AU - Chen, Chih De

AU - Li, Hsin Pai

AU - Luo, Ji Dung

AU - Tan, Bertrand Chin Ming

AU - Chan, Timothy En Haw

AU - Hsueh, Chuen

AU - Chu, Lichieh Julie

AU - Chen, Yi Ting

AU - Zhang, Bing

AU - Yang, Chia Yu

AU - Wu, Chih Ching

AU - Hsu, Chia Wei

AU - See, Lai Chu

AU - Tang, Petrus

AU - Yu, Jau Song

AU - Liao, Wei Chao

AU - Chiang, Wei Fan

AU - Rodriguez, Henry

AU - Myers, Jeffrey N.

AU - Chang, Kai Ping

AU - Chang, Yu Sun

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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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U2 - 10.1038/s41467-017-00493-9

DO - 10.1038/s41467-017-00493-9

M3 - 文章

C2 - 28878238

AN - SCOPUS:85028934689

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

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ER -

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

Abstract

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