In this section
@article{Su:2021:10.1101/gad.345454.120,
author = {Su, XA and Ma, D and Parsons, JV and Replogle, JM and Amatruda, JF and Whittaker, CA and Stegmaier, K and Amon, A},
doi = {10.1101/gad.345454.120},
journal = {Genes Dev},
pages = {556--572},
title = {RAD21 is a driver of chromosome 8 gain in Ewing sarcoma to mitigate replication stress.},
url = {http://dx.doi.org/10.1101/gad.345454.120},
volume = {35},
year = {2021}
}
TY - JOUR
AB - Aneuploidy, defined as whole-chromosome gain or loss, causes cellular stress but, paradoxically, is a frequent occurrence in cancers. Here, we investigate why ∼50% of Ewing sarcomas, driven by the EWS-FLI1 fusion oncogene, harbor chromosome 8 gains. Expression of the EWS-FLI1 fusion in primary cells causes replication stress that can result in cellular senescence. Using an evolution approach, we show that trisomy 8 mitigates EWS-FLI1-induced replication stress through gain of a copy of RAD21. Low-level ectopic expression of RAD21 is sufficient to dampen replication stress and improve proliferation in EWS-FLI1-expressing cells. Conversely, deleting one copy in trisomy 8 cells largely neutralizes the fitness benefit of chromosome 8 gain and reduces tumorgenicity of a Ewing sarcoma cancer cell line in soft agar assays. We propose that RAD21 promotes tumorigenesis through single gene copy gain. Such genes may explain some recurrent aneuploidies in cancer.
AU - Su,XA
AU - Ma,D
AU - Parsons,JV
AU - Replogle,JM
AU - Amatruda,JF
AU - Whittaker,CA
AU - Stegmaier,K
AU - Amon,A
DO - 10.1101/gad.345454.120
EP - 572
PY - 2021///
SP - 556
TI - RAD21 is a driver of chromosome 8 gain in Ewing sarcoma to mitigate replication stress.
T2 - Genes Dev
UR - http://dx.doi.org/10.1101/gad.345454.120
UR - https://www.ncbi.nlm.nih.gov/pubmed/33766983
VL - 35
ER -
For any enquiries related to the MRC Centre please contact:
Scientific Manager
Susannah Fisher
mrc.gida@imperial.ac.uk
External Relationships and Communications Manager
Dr Sabine van Elsland
s.van-elsland@imperial.ac.uk