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B-Myb Induces APOBEC3B Expression Leading to Somatic Mutation in Multiple Cancers
Wen-Cheng Chou1, Wei-Ting Chen1, Chia-Ni Hsiung1
1Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Scientific Reports
|March 10, 2017
Summary
The B-Myb protein drives DNA mutations in cancer by activating APOBEC3B (A3B). Targeting the EGF receptor may suppress this mutagenesis, offering a potential therapeutic strategy for cancer treatment.
Area of Science:
- Genomics
- Molecular Biology
- Cancer Research
Background:
- Cancer genomes accumulate DNA mutations, with cytosine-to-thymine (C-to-T) transitions being the most frequent.
- The cytosine deaminase APOBEC3B (A3B) is implicated in C-to-T transitions, but its regulatory mechanisms remain unclear.
Purpose of the Study:
- To elucidate the mechanism by which APOBEC3B (A3B) is upregulated in cancer.
- To investigate the role of B-Myb in promoting C-to-T transitions and DNA hypermutation.
Main Methods:
- Analysis of The Cancer Genome Atlas (TCGA) database.
- Investigating the binding of B-Myb to the A3B promoter.
- Assessing the effect of EGF receptor blockade with afatinib on B-Myb-A3B signaling.
Main Results:
- B-Myb (MYBL2) binds the A3B promoter, leading to transactivation and C-to-T transitions in breast cancer cells.
- TCGA analysis confirmed MYBL2 and A3B upregulation across multiple cancer types, correlating with C-to-T transitions.
- Afatinib treatment attenuated B-Myb-A3B signaling, reducing mutagenesis.
Conclusions:
- B-Myb-A3B signaling is a significant contributor to DNA damage and mutagenesis in cancer.
- Targeting the EGF receptor presents a potential therapeutic avenue for suppressing B-Myb-A3B-mediated mutagenesis.
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