Recurrent Genomic Alterations in Soft Tissue Perineuriomas.

Area of Science:

• Oncology
• Genetics
• Molecular Pathology

Background:

• Perineuriomas are rare nerve sheath tumors with intraneural and extraneural (soft tissue) subtypes.
• Intraneural perineuriomas often harbor TRAF7 mutations, while chr22q12 deletions are rare.
• Comprehensive molecular profiling of soft tissue perineuriomas, including TRAF7 status, is largely unreported.

Purpose of the Study:

• To conduct high-resolution molecular profiling of soft tissue perineuriomas.
• To investigate chromosomal abnormalities and identify recurrent genetic alterations.
• To compare molecular profiles with intraneural perineuriomas and understand pathogenetic mechanisms.

Main Methods:

• Whole-exome sequencing (WES) and OncoScan single nucleotide polymorphism (SNP) array analysis were performed on 14 soft tissue perineurioma samples.
• Analysis focused on identifying chromosomal deletions, duplications, and mutations.
• Data were correlated with patient demographics, histology, and anatomic site.

Main Results:

• Thirteen of 14 cases exhibited two or more chromosomal abnormalities, primarily large deletions.
• Recurrent, mutually exclusive deletions of chr22q (involving NF2) and chr17q (involving NF1) were identified in 6 and 4 cases, respectively.
• No TRAF7 mutations were found; chr2, chr6, chr7 chromothripsis, and chr10 deletions were also observed in subsets of cases.

Conclusions:

• Recurrent chr22q (NF2) and chr17q (NF1) deletions are key, mutually exclusive events in soft tissue perineurioma pathogenesis.
• Alterations in NF1 or NF2 likely play a significant role, similar to other nerve sheath tumors.
• The absence of TRAF7 mutations suggests distinct molecular pathways compared to intraneural perineuriomas.