Genetic Markers of Peripheral Nerve Tumors: Results From the UCSF500 Cancer Gene Panel

INTRODUCTION: The purpose of the UCSF 500 test is to identify genetic mutations in the DNA of a patient’s cancer. The UCSF 500 test results also provide information on genetic changes that are inherited and increase the risk of developing cancer for a patient or a patient’s family. We report an institutional experience of UCSF500 results from peripheral nerve tumor samples. METHODS: The UCSF 500 Cancer Gene Test uses capture-based next-generation sequencing to target and analyze the coding regions (exons) of 529 cancer genes, as well as select introns of 47 genes. This test can be ordered on solid tumors, hematopoietic malignancies, or lesional tissue specimens. A retrospective analysis of patients with schwannoma, malignant peripheral nerve sheath tumors (MPNST), neurofibroma, and other types of peripheral nerve tumors was performed. RESULTS: 178 samples from 163 patients with peripheral nerve tumors undergoing genetic testing met inclusion criteria. The top 5 mutated genes and their frequency for Neuroblastoma includes PIK3C2G (1.0), IGF1R (0.2), NOTCH2 (0.2), CIC (0.2), ATR (0.2). The 5 genes with the highest frequency copy number alteration (CNA) include SOX9, SRSF2, PRKAR1A, PRKCA, PPM1D. Schwannoma: NF2 (0.58), LZTR1 (0.21), MSH2 (0.14), FAT3 (.13), SMARCB1 (0.1). The top 5 CNA genes were all deletions on chromosome 22. MPNST: TYK2 (1.0), MRE11 (1.0), NF1 (0.65), SUZ12 (0.33), TP53 (0.32). Neurofibroma: TNFAIP3 (1.0), ADGRA2 (1.0), FLT4 (1.0), NF1 (0.61), PRKCH (0.11). Other: TERT (0.39), DDR1 (0.25), KMT2C (0.25), FAT1 (0.15), NRG1 (0.13). CONCLUSIONS: We describe an institutional experience with UCSF500 genetic test results on all peripheral nerve tumors sent for analysis from 2015 to 2022. Using these data to guide the development of understudied genes of interest could lead to increased understanding of the genetic mechanism of these tumors.