Volume 102 Issue 7, July 2022

Pleomorphic xanthoastrocytomas (PXAs) are rare tumors having a heterogenous morphology and biological behavior. Recent genomic advances have discovered BRAFp.V600E mutations, CDKN2A/B deletions and TERTp mutations to be the most frequent alterations in PXAs. These tumors can present a diagnostic challenge as they share overlapping histopathological, genomic as well as methylation profile with various other tumor types. This review provides the spectrum of evolution of PXAs from their genesis to recent molecular insights and attempts to review pathogenesis and relationship to other tumors that they mimic.

This study highlights a novel therapeutic target for glioma. Long noncoding RNA highly upregulated in liver cancer (HULC) stabilizes forkhead box M1 (FOXM1) to upregulate the expression of anterior gradient 2 (AGR2) and hypoxia-inducible factor-1α (HIF-1α), thereby promoting glycolysis and stemness of glioma stem cells and eventually accelerating the development of glioma.

There is a lack of blood biomarkers to diagnose glioblastoma (GBM) patients. This retrospective pilot study aims to determine cell-free microRNAs (cfmiRs) in plasma samples from primary and recurrent GBM patients. Thus, 142 plasma and tissue samples were analyzed using the HTG miRNA whole transcriptome assay (WTA). By combining bioinformatic analysis and receiver operating characteristic curves, we showed that cfmiR-3180-3p and cfmiR-5739 have potential utility in primary and recurrent GBM diagnosis.

The authors demonstrate that carnitine palmitoyltransferase 1A (CPT1A) expression is reduced in glioma stem cells (GSCs) in comparison with non-stem tumor cells. CPT1A overexpression promotes mitochondrial fusion and GSC differentiation by increasing the phosphorylation of dynamin-related protein 1 (Drp1) at Ser-637, thus impairing GSC-derived xenograft growth and prolonging survival in tumor-bearing mice. These results suggest that CPT1A could be a molecular target for GSC differentiation therapy.

Multiplexed ion beam imaging by time-of-flight (MIBI-TOF) uses secondary ion mass spectrometry to image dozens of proteins simultaneously in the same tissue section. The authors undertook a validation study, assessing concordance across serial sections of a tissue microarray that were independently imaged by MIBI-TOF or single-plex immunohistochemistry. They demonstrate that MIBI-TOF can generate consistent and quantitative annotations of clinically relevant cell states in archival human tissue and present a scalable framework for benchmarking multiplexed immunohistochemical approaches.

Siglec-15 is normally expressed by myeloid cells and upregulated in some human cancers and represents a promising new target for immunotherapy. The aim of this study was to develop an immunohistochemical assay for Siglec-15 to be used as a companion diagnostic for future clinical trials. Here, the authors created and validated an assay with a novel recombinant antibody to the cytoplasmic domain of Siglec-15. This study may support development of a companion diagnostic assay to enrich for patients expressing the Siglec-15 target for therapy.