Purpose of review: There are several well-characterized hereditary syndromes that predispose to the development of tumors of the nervous system, and that result from germline mutations in high-penetrance genes. In this review, we provide a brief overview of these syndromes.
Recent findings: The elucidation of the molecular basis of hereditary syndromes has greatly contributed to our understanding of the pathogenesis of human neoplasms. Signaling pathways involved in hereditary syndromes predisposing to the development of nervous system tumors include RAS, WNT, RB1, TP53, and PTCH signaling pathways, which play key roles in gene regulation, apoptosis, and cell proliferation. The discovery of the genetic origin of nervous system tumors in patients with familial cancer syndromes has been the basis for target identification and drug development. This process has resulted in exciting novel and innovative therapeutic approaches. We also briefly review two important advances in this area: the treatment of medulloblastomas in patients with mutations in the PTCH1 gene, and the discovery of deregulated mammalian target of rapamycin as a major oncogenic driver molecule in patients with TSC mutations and subependymal giant cell astrocytoma.
Summary: Progress in the understanding of hereditary nervous system tumors is increasingly important for diagnosis and treatment.