Somatic mutations that inappropriately activate Ras signaling or related signaling pathways can likewise confer proliferation and survival phenotypes to subsets of cells and cause neurological disease. For example, a gain-of-function somatic mutation in GNAQ, encoding G protein subunit alpha q, can lead to Sturge-Weber syndrome, a disease characterized by vascular anomaly in the brain, glaucoma, seizures, stroke, and intellectual disability (53). The same GNAQ mutation, occurring in a different somatic cell type later in development, can cause uveal melanoma (54). Because mutations in certain neurodevelopmental disorders (e.g., neurofibromatosis, tuberous sclerosis, Proteus syndrome, and other neurocutaneous disorders) either activate proto-oncogenes or inactivate tumor suppressor genes, it is not surprising that similar mutations in non-neuronal cell types manifest as cancers. Intriguingly, postmitotic neurons are rarely the source of brain tumors, suggesting that postmitotic neurons may have safeguards that ensure against dedifferentiation and further proliferation.
