Dr. Shen, Chen-Yang 's publons link picture

Dr. Shen, Chen-Yang

Distinguished Research Fellow
  • 02-27899036 (Lab) (Room No: N143)
  • 02-27823047 (Fax)

  • Molecular Epidemiology
  • Cancer Genetics
  • Personalized Medicine

Education and Positions:
  • Ph.D. Univ. of North Carolina at Chapel Hill

Highlight Detail

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

Dr. Shen, Chen-Yang
Scientific Reports, Mar 09, 2017

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.