New research in SciSignal probes the genetic roots of some cases of UvealMelanoma in cells and mice, and points to potential treatment targets for this aggressive and invasive form of eye cancer.
Uveal melanoma is an aggressive form of cancer that arises in the eye and lacks treatment options when it has become metastatic—the stage at which many patients with UM is diagnosed. Some UMs have mutations in the gene encoding the phospholipase PLCβ4. Phan. found that these mutations constitutively activated PLCβ4 and related isoforms, and proliferation was increased in melanocytes expressing these mutants.
proteins are frequent in uveal melanoma, the most common eye cancer arising from the uveal tract. A small proportion of uveal melanomas have a D630Y mutation in phospholipase C β4 , an effector of Gα. Here, we found that the D630Y mutation in PLCβ4 results in a high level of constitutive PLCβ4 activity. Mutations at the corresponding position in other PLC isoforms also resulted in constitutive activity, revealing an unrecognized mechanism underlying PLC activation.
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