Comprehensive Allelotype and Genetic Analysis of 466 Human Nervous System Tumors

TLDR

Brain tumors pose a molecular oncology challenge, with diverse nervous system entities exhibiting distinct pathogenic routes and many reported genetic alterations yet numerous genes remain unidentified. The authors perform a comprehensive allelotype analysis of 466 nervous system tumors using loss‑of‑heterozygosity studies with 129 microsatellite markers across the genome, also assessing alterations in EGFR, CDK4, CDKN2A, TP53, DMBT1, NF2, and PTEN. The study uncovers several novel genetic loci associated with brain tumor development, demonstrates relationships between molecular changes and histopathological features, and expands the concept of molecular tumor variants in neuro‑oncology. This catalogue provides a valuable framework for future investigations into the molecular pathways of many types of human central nervous system tumors.

Abstract

Brain tumors pose a particular challenge to molecular oncology. Many different tumor entities develop in the nervous system and some of them appear to follow distinct pathogenic routes. Molecular genetic alterations have increasingly been reported in nervous system neoplasms. However, a considerable number of affected genes remain to be identified. We present here a comprehensive allelotype analysis of 466 nervous system tumors based on loss of heterozygosity (LOH) studies with 129 microsatellite markers that span the genome. Specific alterations of the EGFR, CDK4, CDKN2A, TP53, DMBT1, NF2, and PTEN genes were analyzed in addition. Our data point to several novel genetic loci associated with brain tumor development, demonstrate relationships between molecular changes and histopathological features, and further expand the concept of molecular tumor variants in neuro-oncology. This catalogue may provide a valuable framework for future studies to delineate molecular pathways in many types of human central nervous system tumors.