GRM3 mutations and use thereof for the diagnosis and treatment of melanoma

摘要

Described herein is a G-protein coupled receptor (GPCR)-directed mutational analysis of tumor DNA obtained from melanoma tissue samples. The GPCR gene glutamate receptor, metabotropic 3 (GRM3) was identified as the most highly mutated GPCR gene in this screen. Functional characterization of GRM3 mutants revealed that these mutants promote activation of MEK, anchorage-independent cell growth and metastasis. Thus, provided herein are methods of diagnosing a subject as having melanoma, or susceptible to developing melanoma, by detecting the presence of at least one mutation in GRM3. Also provided are methods of treating a subject with melanoma by detecting the presence of at least one mutation in GRM3 and administering an appropriate therapy. Further provided are methods of selecting a subject diagnosed with melanoma as a candidate for treatment with a GRM3 inhibitor, an MEK inhibitor, or both, by detecting the presence of at least one mutation in GRM3.

主权项

1. A method of diagnosing a subject as having melanoma, or susceptible to developing melanoma, comprising detecting the presence or absence of at least one mutation in the glutamate receptor, metabotropic 3 (GRM3) gene in a skin sample obtained from the subject, wherein the at least one mutation is selected from G1682A, C1829T, G2299A and G2608A (SEQ ID NO: 1), wherein the presence of the at least one mutation indicates the subject has melanoma or is susceptible to developing melanoma.