A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
The shared frameshift mutation landscape of microsatellite-unstable cancers suggests immunoediting during tumor evolution (2020)


Ballhausen, Alexej; Przybilla, Moritz Jakob; Jendrusch, Michael; Haupt, Saskia; Pfaffendorf, Elisabeth; Seidler, Florian; Witt, Johannes; Hernandez, Sanchez Alejandro; Urban, Katharina et al. (2020). The shared frameshift mutation landscape of microsatellite-unstable cancers suggests immunoediting during tumor evolution. Nature Communications, 11, 4740. DOI: 10.1038/s41467-020-18514-5


JYU-tekijät tai -toimittajat


Julkaisun tiedot

Julkaisun kaikki tekijät tai toimittajat: Ballhausen, Alexej; Przybilla, Moritz Jakob; Jendrusch, Michael; Haupt, Saskia; Pfaffendorf, Elisabeth; Seidler, Florian; Witt, Johannes; Hernandez, Sanchez Alejandro; Urban, Katharina; Draxlbauer, Markus; et al.

Lehti tai sarja: Nature Communications

eISSN: 2041-1723

Julkaisuvuosi: 2020

Volyymi: 11

Artikkelinumero: 4740

Kustantaja: Nature Publishing Group

Julkaisumaa: Britannia

Julkaisun kieli: englanti

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

Avoin saatavuus: Open access -julkaisukanavassa ilmestynyt julkaisu

Julkaisukanavan avoin saatavuus: Kokonaan avoin julkaisukanava

Julkaisun avoin saatavuus: Avoimesti saatavilla

Julkaisu on rinnakkaistallennettu (JYX): https://jyx.jyu.fi/handle/123456789/71908


Tiivistelmä

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.


YSO-asiasanat: suolistosyövät; kohdunrungon syöpä; kasvaimet; syöpäsolut; mutaatiot; immunologia; immuunivaste

Vapaat asiasanat: gastrointestinal cancer; tumour immunology


Liittyvät organisaatiot


OKM-raportointi: Kyllä

Alustava JUFO-taso: 3


Viimeisin päivitys 2021-30-04 klo 15:55