Frequent somatic mutations of GNAQ in uveal melanoma and blue nevi

摘要

BRAF and NRAS are common targets for somatic mutations in benign and malignant neoplasms that arise from melanocytes situated in epithelial structures and lead to constitutive activation of the MAP-kinase pathway^, . However, BRAF and NRAS mutations are absent in a number of other melanocytic neoplasms in which the equivalent oncogenic events are currently unknown. We report frequent somatic mutations in the heterotrimeric G protein alpha subunit, GNAQ, in blue nevi (83%) and ocular melanoma of the uvea (46%). The mutations occur exclusively in codon 209 in the ras-like domain and result in constitutive activation, turning GNAQ into a dominant acting oncogene. Our results demonstrate an alternative route to MAP-kinase activation in melanocytic neoplasia providing new opportunities for therapeutic intervention.