Immune evasion impacts the landscape of driver genes during cancer evolution.
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Embargo End Date
ICR Authors
Authors
Gourmet, L
Sottoriva, A
Walker-Samuel, S
Secrier, M
Zapata, L
Sottoriva, A
Walker-Samuel, S
Secrier, M
Zapata, L
Document Type
Journal Article
Date
2024-06-26
Date Accepted
2024-06-06
Abstract
BACKGROUND: Carcinogenesis is driven by interactions between genetic mutations and the local tumor microenvironment. Recent research has identified hundreds of cancer driver genes; however, these studies often include a mixture of different molecular subtypes and ecological niches and ignore the impact of the immune system. RESULTS: In this study, we compare the landscape of driver genes in tumors that escaped the immune system (escape +) versus those that did not (escape -). We analyze 9896 primary tumors from The Cancer Genome Atlas using the ratio of non-synonymous to synonymous mutations (dN/dS) and find 85 driver genes, including 27 and 16 novel genes, in escape - and escape + tumors, respectively. The dN/dS of driver genes in immune escaped tumors is significantly lower and closer to neutrality than in non-escaped tumors, suggesting selection buffering in driver genes fueled by immune escape. Additionally, we find that immune evasion leads to more mutated sites, a diverse array of mutational signatures and is linked to tumor prognosis. CONCLUSIONS: Our findings highlight the need for improved patient stratification to identify new therapeutic targets for cancer treatment.
Citation
Genome Biology, 2024, 25 (1), pp. 168 -
Source Title
Genome Biology
Publisher
BMC
ISSN
1474-7596
eISSN
1474-760X
Collections
Research Team
Evol Genomics & Modelling
Evolutionary Immunogenomics
Evolutionary Immunogenomics