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@ARTICLE{Ballhausen:163651,
author = {A. Ballhausen$^*$ and M. J. Przybilla$^*$ and M.
Jendrusch$^*$ and S. Haupt and E. Pfaffendorf$^*$ and F.
Seidler$^*$ and J. Witt$^*$ and A. Hernandez Sanchez$^*$ and
K. Urban$^*$ and M. Draxlbauer$^*$ and S. Krausert$^*$ and
A. Ahadova$^*$ and M. S. Kalteis$^*$ and P. Pfuderer$^*$ and
D. Heid$^*$ and D. Stichel$^*$ and J. Gebert$^*$ and M.
Bonsack$^*$ and S. Schott and H. Bläker and T. Seppälä
and J.-P. Mecklin and S. Ten Broeke and M. Nielsen and V.
Heuveline and J. Krzykalla$^*$ and A. Benner$^*$ and A.
Riemer$^*$ and M. von Knebel Doeberitz$^*$ and M. Kloor$^*$},
title = {{T}he shared frameshift mutation landscape of
microsatellite-unstable cancers suggests immunoediting
during tumor evolution.},
journal = {Nature Communications},
volume = {11},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2020-01929},
pages = {4740},
year = {2020},
note = {#EA:F210#LA:F210#},
abstract = {The immune system can recognize and attack cancer cells,
especially those with a high load of mutation-induced
neoantigens. Such neoantigens are abundant in DNA mismatch
repair (MMR)-deficient, microsatellite-unstable (MSI)
cancers. MMR deficiency leads to insertion/deletion (indel)
mutations at coding microsatellites (cMS) and to
neoantigen-inducing translational frameshifts. Here, we
develop a tool to quantify frameshift mutations in MSI
colorectal and endometrial cancer. Our results show that
frameshift mutation frequency is negatively correlated to
the predicted immunogenicity of the resulting peptides,
suggesting counterselection of cell clones with highly
immunogenic frameshift peptides. This correlation is absent
in tumors with Beta-2-microglobulin mutations, and
HLA-A*02:01 status is related to cMS mutation patterns.
Importantly, certain outlier mutations are common in MSI
cancers despite being related to frameshift peptides with
functionally confirmed immunogenicity, suggesting a possible
driver role during MSI tumor evolution. Neoantigens
resulting from shared mutations represent promising vaccine
candidates for prevention of MSI cancers.},
cin = {F210 / B300 / F130 / C060},
ddc = {500},
cid = {I:(DE-He78)F210-20160331 / I:(DE-He78)B300-20160331 /
I:(DE-He78)F130-20160331 / I:(DE-He78)C060-20160331},
pnm = {316 - Infections and cancer (POF3-316)},
pid = {G:(DE-HGF)POF3-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32958755},
doi = {10.1038/s41467-020-18514-5},
url = {https://inrepo02.dkfz.de/record/163651},
}