Use of erbb4 as a prognostic and therapeutic marker for melanoma

Abstract

Members of the protein tyrosine kinase (PTK) family are highly mutated in patients with melanoma. Described herein are novel somatic mutations in the ERBB4 gene that result in increased kinase activity, transformation ability and anchorage-independent growth. These ERBB4 mutations contribute to the tumorogenicity of melanoma. Provided is a method of predicting the prognosis of a patient with melanoma by detecting the presence or absence of a mutation in the ERBB4 gene. In some examples, the ERBB4 mutation is selected from G949A, G1354A, G1624A, C1630T, G1687A, G2506A and G2614A (numbering based on SEQ ID NO: 1). Also provided are methods of selecting a patient as a candidate for treatment with an ERBB4 and/or PI3K/AKT pathway inhibitor, and a method of identifying a therapeutic agent for the treatment of a subject diagnosed with melanoma. Oligonucleotides that specifically hybridize with an ERBB4 nucleic acid molecule comprising a novel mutation are also provided.

1 . A method of detecting a mutation in the ERBB4 gene that is associated with a poor prognosis of a subject diagnosed with melanoma, comprising detecting the presence of a mutation in the ERBB4 gene in a melanoma sample from the subject, wherein the mutation is selected from G949A, G1354A, G1624A, C1630T, G1687A, G2506A and G2614A (numbered with reference to SEQ ID NO: 1). 
     
     
         2 . The method of  claim 1 , wherein the poor prognosis is an increase in the likelihood of death. 
     
     
         3 . The method of  claim 1 , wherein the poor prognosis is an increase in the likelihood of metastasis. 
     
     
         4 . The method of  claim 1 , wherein the mutation in the ERBB4 gene results in an increase in kinase activity of the ERBB4 protein. 
     
     
         5 . The method of  claim 1 , further comprising obtaining the melanoma sample from the subject.