Mutational Signatures and Immune Response in Cancer

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Background

Mutational signatures are characteristic combinations of mutation types arising from specific mutational processes, such as DNA replication infidelity, carcinogens and endogenous cellular mutations, DNA repair deficiency, and enzymatic DNA editing. The accumulating mutations are not homogeneously distributed across the cancer genome, with several epigenetic and genetic markers, such as histone modifications, open chromatin, replication timing, transcription factor binding sites, non-B DNA motifs, as well as gene features, such as exonic and intronic regions, all influencing the likelihood of mutagenesis. The analysis of the activity of these mutational processes in the cancer genome provides insights to the active biological mechanisms that drive it. In addition, the tumor’s immune microenvironment is extremely complex, as virtually all immune cell types can infiltrate the cancer tissue. There, the mutated cancer cells produce further cancer neoantigens, which are likely encountered by the immune system to be eliminated.

Computational analyses of somatic mutation data in cancer genomes have provided a wealth of information on the mutagenic processes. However, the aetiology of many mutational patterns and their relationship with the immunological response within the tumor microenvironment (TME), remain unknown or not fully understood. For example, cancer cells within the TME respond differently to various types of immunotherapies, based on their molecular profile or the TME’s immunological profile. It remains however, unclear how the tumor’s immune microenvironment influences the accumulation, location and frequency of somatic mutations. Studies that combine work in the role of the TME and its relationship with the distribution of different mutation types across genomic and epigenetic features could provide a better understanding on the tumor’s vulnerabilities. Therefore, a better understanding of these mutational patterns in the setting of the TME and combination with genomic and epigenetic co-factors could provide further therapeutic opportunities for cancer patients.

The scope of this Research Topic is to evaluate our current knowledge on the existence of the different mutational signatures in the cancer genome and how they could be applied for diagnostic purposes. Contributors are thus, encouraged to submit original research and review articles that use existing approaches providing further insight into the mutation patterns in the TME in different types of cancer, and/or how these could lead to resistance to immunotherapies.

The Topic Editors encourage authors to submit papers having a requirement of at least one independent validation cohort if no experimental data is communicated. Submissions based on the analysis of solely one database e.g. TCGA will not be considered for publication.

Keywords: Mutational signatures, tumor immune, microenvironment, inflammation, epigenetic markers, replication, non-B DNA motifs, transcription factors, neoantigens

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