M. Renzetti1, I. Soliman1, H. Wu1, B. Luo1, H. Liu1, A. Olszanski1, S. Movva1, M. Lango1, S. Reddy1, F. Zih1, J. M. Farma1 1Fox Chase Cancer Center,Surgical Oncology,Philadelphia, PA, USA
Introduction: The use of next generation sequencing (NGS) molecular profiling has become increasingly important in providing valuable prognostic information on primary cancers with the potential to uncover actionable mutations. Our institution has been using NGS to examine mutations in 50 cancer-related genes. Here we examine molecular profiling of melanoma patients who were classified as Class 2 based on the MelanomaDx test.
Methods: Melanoma patients who underwent both NGS and Melanoma Dx GEP testing, and were Class 2 were evaluated. Using NGS, we analyzed malignant melanoma (MM) tissue samples for somatic mutations in targeted regions of 50 common cancer related genes. We generally order this testing on advanced melanoma patients. Tissue samples were also sent for the Melanoma Dx test. Clinical and pathologic data were collected.
Results: We performed NGS on 133 patients with MM, and 18 of those patients also underwent MelanomaDx GEP testing and 15 were Class 2. In Class 2 patients, median age at diagnosis was 66 years (range 27-79) and 80% were male (n=12). Median follow up was 2 months (range 1-27). Location of the primary included upper extremity (n=4), trunk (n=4), and lower extremity (n=7). At presentation, 2 MM were stage I, 13 were stage II. All Class 2 tissue samples were taken from primary tumors. In total, 22 mutations were identified, affecting 12 unique genes. No mutations were found in 13.3% of patients (n=2), 33.3% had one mutation (n=5), 46.7% had 2 mutations (n=7), and 6.7% had 3 mutations (n=1). The most frequently identified mutations were BRAF (n=4), CDKN2A (n=3), NRAS (n=4), and TP53 (n=3) (Fig. 1).
40% of the patients had a MM recurrence (n=6), 83.3% of which had distant metastasis (n=5). Median time to recurrence was 16 months (range 9-53). Recurrent melanomas had 10 mutations over 7 unique genes. 4 patients had 2 gene mutations, and 2 only had 1. Most common gene mutations were BRAF (n=2) and NRAS (n=3).
Conclusion: Using both our NGS platform and MelanomaDx GEP for Class 2 MM patients, we identified that the most common mutations in both recurrent and nonrecurrent MM are BRAF and NRAS in 22.2% of patients each. Future studies will identify and correlate specific molecular profile patterns with treatment response and survival outcomes.
