Synovial Sarcoma With BRAF V600E Mutation: A Case Report and Literature Review

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Synovial sarcoma (SS) is a soft tissue sarcoma defined by the SS18::SSX fusion.
• SS typically has few secondary genomic alterations.
• Metastatic SS often presents challenges in treatment.

Purpose of the Study:

• To report a case of metastatic SS with an SS18::SSX1 rearrangement and a BRAF V600E mutation.
• To investigate the potential of targeted therapy for SS harboring BRAF V600E.
• To highlight the utility of comprehensive genomic profiling in advanced SS.

Main Methods:

• Next-generation sequencing (DNA and RNA) for comprehensive genomic profiling.
• Fluorescence in situ hybridization (FISH) to confirm SS18 rearrangement.
• Immunohistochemistry to support histologic diagnosis.
• Literature review to identify additional SS cases with BRAF V600E.

Main Results:

• A patient with metastatic SS was found to have both SS18::SSX1 and BRAF V600E.
• Treatment with dabrafenib and trametinib (BRAF and MEK inhibitors) led to a clinical response.
• Literature search revealed multiple SS cases with BRAF V600E, indicating it's a recurrent alteration.

Conclusions:

• BRAF V600E is a recurrent, potentially targetable molecular alteration in a subset of synovial sarcoma.
• Comprehensive genomic profiling is valuable for identifying actionable mutations in advanced or refractory SS.
• Targeted therapy, such as BRAF/MEK inhibition, can offer therapeutic options for specific SS molecular subtypes.