M. Renzetti1, I. Solimon1, K. Loo1, E. Lamb1, H. Wu1, B. Luo1, H. Liu1, A. Olszanski1, S. Movva1, M. Lango1, S. Reddy1, J. 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 characterizing cancers and their subtypes. Our institution has been using NGS to examine mutations in 50 cancer-related genes. It is well established that the nodular subtype of malignant melanoma (MM) tend to be more invasive, ulcerated, and have more mitoses than superficial spreading subtype (SS). Here we examine the use of molecular profiling of patients who presented with either SS or nodular type MM.
Methods: Patients with either SS or nodular type MM 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: We performed NGS on 179 patients with MM. Of these, 51 patients presented with nodular type MM, and 46 with SS type. Median age at diagnosis was 64 for nodular and 59 for SS (range 22-81). 65.3% and 74% were male in nodular and SS respectively. Location of the primary included head and neck (8 nodular, 4 SS), upper extremity (15 nodular, 11 SS), lower extremity (11 nodular, 10 SS) and truncal (17 nodular, 21 SS). At presentation, 2 nodular and 7 SS were stage I, 19 nodular and 7 SS were stage II, 26 nodular and 31 SS were stage III, and 4 nodular and 1 SS were stage IV. Of the tissue tested, 53% (n=51) were from the primary tumor. In the nodular type, 86 total mutations were identified over 43 unique genes, and in SS type, 73 mutations were identified affecting 35 unique genes (p = 0.34).
In nodular type, no mutations were found in 16% of patients (n=8), while 43% of patients (n=13) had one mutation, 24% (n=12) had 2 mutations, 14% (n=7) had 3 mutations, and 10% (n=5) had 4 or more mutations. The most frequently identified mutations included NRAS (33%, n=17), BRAF V600E (29%, n=15), TP53 (22%, n=11), CDKN2A (10%, n=5), and CTNNB1 (8%, n=4).
In SS type, no mutations were found in 2% of patients (n=1), while 61% of patients (n=28) had only one mutation, 24% (n=11) had 2 mutations, 7% (n=3) had 3 mutations, and 7% (n=3) had 4 or more mutations. The most frequently identified mutations were NRAS (35%, n=16), BRAF V600E (33%, n=15), TP53 (17%, n=8), BRAF V600R (11%, n=5), and PTEN (11%, n=5). There was no significant difference in the molecular profiles between nodular and SS types.
Conclusion:We found that the most frequent mutations in nodular melanomas were NRAS, BRAF V600E, TP53, CDKN2A, and CTNNB1, and the most frequent superficial spreading mutations were NRAS, BRAF V600E, TP53, BRAF V600R, and PTEN. It appeared to be more common to have no mutation in nodular melanoma. Future studies will further identify mutation patterns in MM subtypes and correlate them with treatment response.
