RASopathy syndromes: Understanding signaling pathway disorders leading to tumorigenesis.

This article describes the family of RAS genes, their role in encoding groups of proteins known as RAS proteins, and a group of genetic disorders known as RASopathy syndromes. RAS genetic disorders are associated with unregulated cell growth, differentiation, and irregularities in apoptosis leading to tumorigenesis. More than 30% of all human cancers are driven by mutations in RAS genes. There are a number of genetic disorders, known as RASopathies, that are considered potential cancer syndromes, as they predispose individuals to development of benign or malignant neoplasms. This article describes the genetic mutations in RAS genes that affect RAS protein production, creating cell signaling pathway abnormalities and leading to tumor formation. Neurofibromatosis type 1 (NF1) is used as an example of how a RASopathy disorder leads to multisystem disease sequelae. Finally, the role of MEK inhibitors in disrupting abnormal cell signaling is described in their use with NF1 plexiform neurofibromas and their emerging roles in cancer treatment.