PLCB4
Overview
PLCB4 encodes phospholipase C beta 4, a downstream effector of Gαq/11 signaling. In uveal melanoma, PLCB4 carries a recurrent hotspot mutation p.D630Y that is distinct from its mutational pattern in cutaneous melanoma. The D630Y allele acts downstream of GNAQ/GNA11 mutations and is proposed to be a gain-of-function driver in uveal melanoma, placing PLCB4 as both an oncogene (in uveal melanoma) and a potential tumor suppressor (in cutaneous melanoma) in a context-dependent manner.
Alterations observed in the corpus
- Recurrent hotspot p.D630Y (c.G1888T) in 2/28 uveal melanoma samples, mutually exclusive with GNAQ/GNA11; proposed gain-of-function driver in uveal melanoma. Contrasts with cutaneous melanoma where PLCB4 is mutated in 21–28% of cases along the length of the gene without recurrence at p.D630, suggestive of a loss-of-function role in cutaneous melanoma PMID:26683228
Cancer types (linked)
- UVM (Uveal Melanoma): Recurrent hotspot p.D630Y in ~7% of cases (2/28); mutually exclusive with GNAQ/GNA11; identified as an alternative driver within the Gαq pathway PMID:26683228
Co-occurrence and mutual exclusivity
- Mutually exclusive with GNAQ (p.Q209P, p.G48L) and GNA11 (p.Q209P) mutations in uveal melanoma, consistent with all three genes acting in the same pathway PMID:26683228
Therapeutic relevance
- PLCB4-mutant uveal melanoma tumors should be considered functionally equivalent to GNAQ/GNA11-mutant tumors for pathway-targeted therapeutic strategies PMID:26683228
Open questions
- Functional validation of PLCB4 p.D630Y as gain-of-function has not been performed; the authors call for functional studies PMID:26683228
- The mechanistic basis for the tissue-specific role of PLCB4 as oncogene in uveal melanoma vs. potential tumor suppressor in cutaneous melanoma remains unexplained PMID:26683228
Sources
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