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The role of aneuploidy in tumorigenesis.

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  • UserProfessor Angelika Amon, MIT, Department of Biology, Cambridge, MA, USA
  • ClockThursday 22 October 2020, 14:00-15:00
  • HouseZoom meeting.

If you have a question about this talk, please contact Caroline Newnham.

Host: Marco Geymonat

RAD21 is a driver of chromosome 8 gain in Ewing sarcoma to enhance DNA repair

Marianna Trakala, Xiaofeng A. Su and Angelika Amon

David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139 .

Aneuploidy, defined as whole chromosome gain or loss, causes cellular stress but, paradoxically, is a frequent occurrence in cancers. Whether or not aneuploidy contributes to tumorigenesis is however controversial, with some mouse models of chromosome instability being tumor prone but others not. We investigated the role of aneuploidy in tumorigenesis and found that it causes tumorigenesis with high penetrance when aneuploidy levels are sufficiently high in organisms. Furthermore, we examined the basis for recurrent aneuploidies in cancer. For example, 50% of Ewing sarcomas, a pediatric bone and soft tissue tumor driven by the EWS -FLI1 fusion oncogene harbor chromosome 8 gains. We investigated why this is the case. We found that trisomy 8 enhances repair of EWS -FLI1 induced DNA damage through gain of a copy of RAD21 , thereby improving proliferation of EWS -FLI1 expressing cells. Our data further indicate that RAD21 acts within a narrow, low level overexpression range to promote tumorigenesis. We propose that RAD21 is the founding member of a new class of tumorigenesis promoting genes. Such genes may drive recurrent aneuploidies in cancer.

This talk is part of the Genetics Seminar series.

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