J. Lou1, M. Renzetti1, I. Soliman1, H. Wu1, B. Luo1, A. J. Olszanski1, S. Movva1, M. Lango1, S. Reddy1, F. Zih1, J. M. Farma1 1Fox Chase Cancer Center,Surgical Oncology,Philadelphia, PA, USA
Introduction: Molecular profiling is becoming an increasingly important aspect in the interrogation of primary cancers. Next generation sequencing (NGS) is being used at our institution to examine hot-spot mutations in 50 cancer-related genes in various tumors. The principle aim of this investigation is to evaluate molecular profiling of malignant melanoma (MM) and to correlate primary location of the melanoma with genetic mutations.
Methods: Patients with primary or recurrent MM of all stages were included in the study. Using NGS, we analyzed tissue samples for mutations in targeted regions of 50 cancer-related genes. Clinical and pathologic data were collected.
Results: Specimens from 138 patients with MM were analyzed, excluding 2 from analysis due to insufficient DNA and 1 due to incomplete profiling. Median age at diagnosis was 65 (range 24-90) and 64% were male (n=86). There were 26 patients with Stage I melanoma, 72 with Stage II, 14 with Stage III, and 12 with Stage IV. Primary tumor locations included head and neck (N=23), upper extremity (N=29), trunk (N=31), lower extremity (N=39), and mucosal sites (N=5). In total, 218 mutations were identified, affecting 30 unique genes. Patients with a primary location at their head and neck had the greatest average number of mutations (x=2.04), with the greatest percentage of mutations in BRAF (including BRAF K601E, G466V, V600E, V600K, V600R) and TP53 genes (Figure 1). Lower extremity sites had the next highest mean number of mutations (x=1.87), with the greatest fraction of mutations in BRAF and NRAS genes (Figure 1). Mucosal tumors had the lowest mean number of mutations (x=0.4), with only mutations in TP53 (Figure 1). Across all sites, a large percentage of mutations were either in BRAF, NRAS, or TP53 genes, with BRAF being the most common in lower extremity sites and NRAS most common in truncal tumors.
Conclusion: While there is no statistical significance comparing primary tumor site and genetic mutations, the descriptive statistics warrants further investigation with a larger sample size.
