B-Myb Induces APOBEC3B Expression Leading to Somatic Mutation in Multiple Cancers

被引：27

作者：

Chou, Wen-Cheng ^{[1
]}

Chen, Wei-Ting ^{[1
]}

Hsiung, Chia-Ni ^{[1
]}

Hu, Ling-Yueh ^{[1
]}

Yu, Jyh-Cherng ^{[2
]}

Hsu, Huan-Ming ^{[2
]}

Shen, Chen-Yang ^{[1
,3
,4
]}

机构：

[1] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan

[2] Triserv Gen Hosp, Dept Surg, Taipei, Taiwan

[3] Acad Sinica, Taiwan Biobank, Taipei, Taiwan

[4] China Med Univ, Coll Publ Hlth, Taichung, Taiwan

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

BREAST; LANDSCAPE; DNA; PATHWAY; MUTAGENESIS; OUTCOMES; REPAIR; GENES;

D O I：

10.1038/srep44089

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The key signature of cancer genomes is the accumulation of DNA mutations, the most abundant of which is the cytosine-to-thymine (C-to-T) transition that results from cytosine deamination. Analysis of The Cancer Genome Atlas (TCGA) database has demonstrated that this transition is caused mainly by upregulation of the cytosine deaminase APOBEC3B (A3B), but the mechanism has not been completely characterized. We found that B-Myb (encoded by MYBL2) binds the A3B promoter, causing transactivation, and this is responsible for the C-to-T transitions and DNA hypermutation in breast cancer cells. Analysis of TCGA database yielded similar results, supporting that MYBL2 and A3B are upregulated and putatively promote C-to-T transitions in multiple cancer types. Moreover, blockade of EGF receptor with afatinib attenuated B-Myb-A3B signaling, suggesting a clinically relevant means of suppressing mutagenesis. Our results suggest that B-Myb-A3B contributes to DNA damage and could be targeted by inhibiting EGF receptor.

引用

页数：11

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