Utility of ret mutant in diagnosis and treatment of melanoma

Abstract

The invention relates to a method of detecting a RET mutant in a melanoma cell. Also disclosed is a method of modulating the activity of a RET mutant in a melanoma cell with an agent that interferes with the activity of the RET mutant.

1 . A method of modulating the activity of a RET mutant in a melanoma cell, comprising:
 providing a melanoma cell containing a RET mutant; and   contacting the cell with an agent that interferes with the activity of the RET mutant.   
     
     
         2 . The method of  claim 1 , wherein the RET mutant is RETmt (RET G691S). 
     
     
         3 . The method of  claim 1 , wherein the melanoma cell further contains a BRAF mutant. 
     
     
         4 . The method of  claim 3 , wherein the BRAF mutant is BRAFmt. 
     
     
         5 . The method of  claim 1 , wherein the agent interferes with the interaction between the RET mutant and GDNF (glial cell line-derived neurotrophic factor). 
     
     
         6 . The method of  claim 1 , wherein the agent interferes with the signal transduction through a pathway comprising the RET mutant and RAS (rat sarcoma). 
     
     
         7 . The method of  claim 6 , wherein the agent interferes with cell proliferation, migration, or invasion, or the phosphorylation of ERK1/2 (Extracellular Signal-Regulated Kinase 1/2). 
     
     
         8 . The method of  claim 1 , wherein the agent interferes with the signal transduction through a pathway comprising the RET mutant and PI3K (phosphatidylinositol-3-Kinase). 
     
     
         9 . The method of  claim 8 , wherein the agent interferes with cell proliferation, migration, or invasion, or the phosphorylation of Akt (protein kinase B). 
     
     
         10 . The method of  claim 1 , wherein the agent is a RTK (receptor tyrosine kinase) inhibitor. 
     
     
         11 . The method of  claim 10 , wherein the RTK inhibitor is sorafenib or semaxanib. 
     
     
         12 . The method of  claim 1 , wherein the agent is an antibody, peptide, or siRNA against the RET mutant.