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CAS Key Laboratory of Computational Biology Seminar: Molecular Mechanism and Clinical Impact of APOBEC Mutagenesis in Cancer (June 8, 2017)
2017-06-03
 

Speaker: Reuben S. Harris, Ph.D.

Howard Hughes Medical Research Institute, Masonic Cancer Center, Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA             

Web: http://harris.cbs.umn.edu/people.html

     

Time: 14:00 pm, 8th June (Thursday) 

Place: Room 300, SIBS Main Building, Yueyang Road 320

Host: Dr. Li Yang

Title: Molecular Mechanism and Clinical Impact of APOBEC Mutagenesis in Cancer

Abstract:

Recent studies have implicated the DNA cytosine deaminase APOBEC3B as a major source of mutation in breast and many other cancer types. APOBEC3B explains a large proportion of both dispersed and clustered cytosine mutations, the latter of which are also called kataegis. APOBEC3B expression levels correlate with poor outcomes for patients with estrogen receptor positive breast cancer. While targeted therapies, such as tamoxifen, are available to treat these tumors, secondary drug resistance often develops. Clinical data will be presented that strongly implicate APOBEC3B in tumor recurrence and resistance to tamoxifen therapy after surgical resection of primary tumors. APOBEC3B knockdown and overexpression experiments were done in a xenograft model for estrogen receptor positive breast cancer. The clinical and experimental results combine to demonstrate that APOBEC3B drives resistance to endocrine treatment with tamoxifen. These results are likely to be broadly applicable to other cancer types and targeted therapies as APOBEC3B is a general source of mutagenic fuel for tumor evolution.


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