title: Novel somatic mutations in heterotrimeric G proteins in melanoma.
abstract: Heterotrimeric guanine nucleotide-binding proteins (G proteins) mediate signals between G-protein coupled receptors and their downstream pathways, and have been shown to be mutated in cancer. In particular, GNAQ was found to be frequently mutated in blue nevi of the skin and uveal melanoma, acting as an oncogene in its mutated form. To further examine the role of heterotrimeric G proteins in malignant melanoma, we performed a comprehensive mutational analysis of the 35 genes in the heterotrimeric G protein gene family in a panel of 80 melanoma samples. Somatic alterations in a G protein subunit were detected in 17% of samples spanning 7 genes. The highest rates of somatic, non-synonymous mutations were found in GNG10 and GNAZ, neither of which has been previously reported to be mutated in melanoma. Our study is the first systematic analysis of the heterotrimeric G proteins in melanoma and indicates that multiple mutated heterotrimeric G proteins may be involved in melanoma progression.
authors.affiliation: Cancer Genetics Branch, National Institutes of Health (NIH); Bethesda, MD, USA.
authors.forename: L Isabel
authors.initials: LI
authors.lastname: Cárdenas-Navia
authors.forename: Pedro
authors.initials: P
authors.lastname: Cruz
authors.forename: Jimmy C
authors.initials: JC
authors.lastname: Lin
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: Yardena
authors.initials: Y
authors.lastname: Samuels
mesh_terms: D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; D020962:Heterotrimeric GTP-Binding Proteins