title: Mutational activation of RAS and GSP oncogenes in differentiated thyroid cancer and their biological implications.
abstract: Activating mutations of ras-genes (Kirsten-ras, Harvey-ras, N-ras) and genes encoding for the alpha subunit of G-proteins (Gs, Gi2, Gi3, Go, Gz) were assessed in 32 differentiated thyroid cancer (DTC) tissues from German (n = 22) and American (n = 10) patients. Gs-protein (GSP) and/or ras mutations were found in 69% of all tissues with a heterogeneous distribution pattern. An increased prevalence could be demonstrated in metastatic (8 of 9 mutation positive) when compared to localized disease (13 of 23 mutation positive) (p less than 0.001) and in patients greater than 50 years of age (16 of 18 mutation positive), when compared to younger patients (6 of 14 mutation positive) (p less than 0.001). No activating mutations were found on H-ras and K-ras genes nor on genes encoding for the alpha subunits of Gi2, Gi3, Go, and Gz. Differentiated thyroid cancer tissue from German patients revealed a higher prevalence for GSP mutations (73%) than did DTC from American patients (20%) (p less than 0.001). We demonstrated a high frequency of ras and GSP mutations in DTC and suggest that these mutations may contribute to our basic understanding of this disease and might initiate a new search for more rational and individualized therapeutic approaches in patients with DTC.
authors.affiliation: Department of Pharmacology, University of California, San Francisco.
authors.forename: P E
authors.initials: PE
authors.lastname: Goretzki
authors.forename: J
authors.initials: J
authors.lastname: Lyons
authors.forename: S
authors.initials: S
authors.lastname: Stacy-Phipps
authors.forename: W
authors.initials: W
authors.lastname: Rosenau
authors.forename: M
authors.initials: M
authors.lastname: Demeure
authors.forename: O H
authors.initials: OH
authors.lastname: Clark
authors.forename: F
authors.initials: F
authors.lastname: McCormick
authors.forename: H D
authors.initials: HD
authors.lastname: Röher
authors.forename: H R
authors.initials: HR
authors.lastname: Bourne
mesh_terms: D001483:Base Sequence; D019204:GTP-Binding Proteins / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D013964:Thyroid Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D019204:GTP-Binding Proteins