APOBEC Mutagenesis in Cancer Development and Susceptibility.

APOBEC cytosine deaminases are prominent mutators in cancer, mediating mutations in over 50% of cancers. APOBEC mutagenesis has been linked to tumor heterogeneity, persistent cell evolution, and therapy responses. While emerging evidence supports the impact of APOBEC mutagenesis on cancer progression, the understanding of its contribution to cancer susceptibility and malignant transformation is limited. We examine the existing evidence for the role of APOBEC mutagenesis in carcinogenesis on the basis of the reported associations between germline polymorphisms in genes encoding APOBEC enzymes and cancer risk, insights into APOBEC activities from sequencing efforts of both malignant and non-malignant human tissues, and in vivo studies. We discuss key knowledge gaps and highlight possible ways to gain a deeper understanding of the contribution of APOBEC mutagenesis to cancer development.

A Toolkit for Profiling the Immune Landscape of Pediatric Central Nervous System Malignancies.

The prognosis of pediatric central nervous system (CNS) malignancies remains dismal due to limited treatment options, resulting in high mortality rates and long-term morbidities. Immunotherapies, including checkpoint inhibition, cancer vaccines, engineered T cell therapies, and oncolytic viruses, have promising results in some hematological and solid malignancies, and are being investigated in clinical trials for various high-grade CNS malignancies. However, the role of the tumor immune microenvironment (TIME) in CNS malignancies is mostly unknown for pediatric cases. In order to successfully implement immunotherapies and to eventually predict which patients would benefit from such treatments, in-depth characterization of the TIME at diagnosis and throughout treatment is essential. In this review, we provide an overview of techniques for immune profiling of CNS malignancies, and detail how they can be utilized for different tissue types and studies. These techniques include immunohistochemistry and flow cytometry for quantifying and phenotyping the infiltrating immune cells, bulk and single-cell transcriptomics for describing the implicated immunological pathways, as well as functional assays. Finally, we aim to describe the potential benefits of evaluating other compartments of the immune system implicated by cancer therapies, such as cerebrospinal fluid and blood, and how such liquid biopsies are informative when designing immune monitoring studies. Understanding and uniformly evaluating the TIME and immune landscape of pediatric CNS malignancies will be essential to eventually integrate immunotherapy into clinical practice.

Neurooncology: 2022 update.

This 'Neurooncology: 2022 update' presents topics that were selected by the authors as top ten discoveries published in 2021 in the broader field of neurooncological pathology. This time, the spectrum of topics includes: papers with a direct impact on daily diagnostic practice of CNS tumors in general and with information on how to improve grading of meningiomas; studies shedding new light on the oncogenesis of gliomas (in particular 'optic gliomas' and H3-mutant gliomas); several 'multi-omic' investigations unraveling the intra-tumoral heterogeneity of especially glioblastomas further; a study indicating the potential of 'repurposing' Prozac® for the treatment of glioblastomas; liquid biopsy using CSF for assessment of residual medulloblastoma. In the last part of this review some other papers are mentioned that didn't make it to this (quite subjective) top ten list.