Genetic Aspects of Peripheral Nervous System Tumors

Abstract

Advances in genetics with the developments in informatics and imaging allowed refining the classification of peripheral nerve tumors, often with important prognostic and treatment implications. In 2016, the World Health Organization (WHO) published an update in which molecular parameters were included for the first time. For these tumors, the major changes included the expansion and clarification of entities included in the section of nerve sheath tumors, with the addition of hybrid nerve sheath tumors and the separation of melanotic schwannoma from other schwannomas. A wide spectrum of genetics and epigenetic aberrations are involved in the growth of malignant cells. Genetic alterations include mutations, genomic instability, loss of heterozygosity (LOH), and gene copy number variation (CNV). Epigenetics changes which regulate gene expression without altering the underlying nucleotide sequence involved histone modifications, DNA methylation, and loss of imprinting (LOI). In hereditary tumors, we can find constitutional alterations associated with somatic loss of function of wild-type alleles. In the corresponding sporadic tumors, biallelic somatic loss-of-function (LOF) mutations can be found. This chapter describes the aforementioned genetic aspects of peripheral nerve tumors.