Uveal Melanocytoma without GNAQ/GNA11 Mutations

Area of Science:

• Ophthalmology
• Oncology
• Genetics

Background:

• Uveal melanocytomas are benign tumors with characteristic cell morphology and common GNAQ/GNA11 mutations.
• GNAQ/GNA11 mutations are frequently found in both benign uveal nevi and malignant uveal melanomas.
• Identifying these mutations aids in diagnosis and prognosis of uveal melanocytic neoplasms.

Purpose of the Study:

• To investigate the molecular underpinnings of a rare uveal melanocytoma case.
• To determine if common GNAQ/GNA11 mutations are present in this specific uveal melanocytoma.
• To explore potential novel molecular drivers in uveal melanocytic proliferations.

Main Methods:

• A patient with a ciliochoroidal mass underwent enucleation.
• Fine needle aspiration (FNA) biopsy and subsequent sequencing of the tumor were performed.
• Genetic analysis included the DecisionDX-UMSeq panel and a broader 197-gene panel (STAMP).

Main Results:

• The uveal melanocytoma lacked GNAQ/GNA11 mutations and other known uveal melanoma driver mutations.
• Sequencing identified novel missense variants of unknown significance in three genes.
• These findings were confirmed across different molecular testing panels.

Conclusions:

• This is the first reported case of uveal melanocytoma without GNAQ/GNA11 mutations.
• The case highlights the existence of alternative molecular pathways in uveal melanocyte proliferation.
• Further research is needed to identify new genes and pathways involved in these neoplasms.