Mutational activation of RAS and GSP oncogenes in differentiated thyroid cancer and their biological implications

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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) (p50 years of age (16 of 18 mutation positive), when compared to younger patients (6 of 14 mutation positive) (pp<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.

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