Frequent ERBB4 mutations in melanoma

Mutations in the gene ERBB4 were found in 19% of metatstatic melanomas, a skin cancer that is often fatal, according to a study published online in this week's Nature Genetics. While early-stage melanoma is often cured by surgery, metastatic melanoma is difficult to treat and is almost always fatal.

Since the protein tyrosine kinase (PTK) genes are frequently mutated in cancer, Yardena Samuels and colleagues sequenced 86 PTK genes in 29 melanomas and found 30 tumor-specific mutations in 19 of the 86 PTK genes. Additional sequencing in 79 more melanoma tumors identified 99 cancer-specific mutations, 19% of which were mutations occurring in the PTK gene ERBB4.

Further experiments showed that the mutations in ERBB4 increased growth of melanoma cells in the lab, but treatment of cells with the pharmacological inhibitor lapitinib reduced melanoma cell growth. The research suggests that targeting ERBB4 with small-molecule inhibitors should be investigated as a therapeutic approach for those with melanomas carrying mutations in this gene.