A1 Journal article (refereed)
The shared frameshift mutation landscape of microsatellite-unstable cancers suggests immunoediting during tumor evolution (2020)


Ballhausen, A., Przybilla, M. J., Jendrusch, M., Haupt, S., Pfaffendorf, E., Seidler, F., Witt, J., Hernandez, S. A., Urban, K., Draxlbauer, M., Krausert, S., Ahadova, A., Kalteis, M. S., Pfuderer, P. L., Heid, D., Stichel, D., Gebert, J., Bonsack, M., Schott, S., . . . Kloor, M. (2020). The shared frameshift mutation landscape of microsatellite-unstable cancers suggests immunoediting during tumor evolution. Nature Communications, 11, Article 4740. https://doi.org/10.1038/s41467-020-18514-5


JYU authors or editors


Publication details

All authors or editors: Ballhausen, Alexej; Przybilla, Moritz Jakob; Jendrusch, Michael; Haupt, Saskia; Pfaffendorf, Elisabeth; Seidler, Florian; Witt, Johannes; Hernandez, Sanchez Alejandro; Urban, Katharina; Draxlbauer, Markus; et al.

Journal or series: Nature Communications

eISSN: 2041-1723

Publication year: 2020

Volume: 11

Article number: 4740

Publisher: Nature Publishing Group

Publication country: United Kingdom

Publication language: English

DOI: https://doi.org/10.1038/s41467-020-18514-5

Publication open access: Openly available

Publication channel open access: Open Access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/71908


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.


Keywords: bowel cancer; endometrial cancer; tumours; cancer cells; mutations; immunology; immune response

Free keywords: gastrointestinal cancer; tumour immunology


Contributing organizations


Ministry reporting: Yes

Reporting Year: 2020

JUFO rating: 3


Last updated on 2021-02-08 at 10:25