L. Selesner1, M. Renzetti1, I. Soliman1, H. Wu1, B. Luo1, A. Olszanski1, S. Movva1, M. Lango1, S. Reddy1, F. Zih1, J. M. Farma1 1Fox Chase Cancer Center,Surgical Oncology,Philadelphia, PA, USA
Introduction: Molecular profiling of primary cancers is becoming an important technique to evaluate and personalize treatment for patients with melanoma. We have investigated mutations in 50 different targetable cancer-related genes using Next Generation Sequencing (NGS). This study uses molecular profiling data to examine the relationship between these mutations and the pathological primary thickness in a cohort of patients with malignant melanoma.
Methods: A retrospective study of a prospective dataset was performed that included patients with both primary and recurrent malignant melanomas (MM). From this cohort of patients, we analyzed tissue samples for somatic mutations in targeted regions of 50 cancer-related genes. Clinical and pathological data was collected. Statistical analysis was performed to identify mutations based on the pathological T stage of the primary tumor. The mean number of mutations per person presenting at each T stage was then investigated.
Results: We collected specimens from 135 patients with melanoma. The median age of diagnosis was 65 years (range 24-90) and 63.7% were male (n=86). At last follow up, 64 had no evidence of disease, 46 were alive with disease, 20 died of disease, 2 died of other causes, and 3 had an unknown status. Of the tissues tested, 4 presented as pathological T stage 1 (3.5%), 26 as T stage II (22.6%), 33 as T stage III (28.7%), and 50 as T stage IV (43.5%). At T stages I, II, III, IV averages of 1.75, 1.19, 1.78 and 1.62 mutations per person were attained (p= 0.44). Among the mutations found, NRAS and BRAF mutations were frequently expressed in each of the T stages. Of the patients presenting as T stage I, 50% had a NRAS mutation (n=2). At T stage II, 30.8% of the patients had a NRAS mutation (n=8). At T stage II, 42.8% had a NRAS mutation (n=14) and at T stage IV, 26% of the patients had the mutation (n=13) (p=0.52). In reference to BRAF, 25% of the T stage I patients (n=1), 34.6% of the T stage II patients (n=9), 24.2% of the T stage III patients (n=8), and 22% of the T stage IV patients (n=11) had a mutation in at least one of the BRAF genes (p=0.71). Also of interest, TP53 was the most common mutation in the patients presenting at T stage IV with 28% of this cohort expressing this mutation (Figure 1).
Conclusion: Using our NGS platform in patients, we identified the most prevalent mutations in our cohort of patients that presented at the four different pathological T stages (I-IV). We found that for T stage I, the most frequent mutation was in NRAS. For T stages II and III, mutations in NRAS and at least one of the BRAF genes, were expressed in the highest number. Finally, TP53 and NRAS mutations were most common in the T stage IV patients. While there was no statistical significance found comparing the pathological T stage and genetic mutations, the data warrants further investigation with a larger sample size.
