Genomic Profiling Of Melanomas Of Unknown Primary.

e21048 Background: Approximately 2-10% of metastatic melanoma patients present without an identifiable primary melanocytic lesion. These melanomas of unknown primary (MUP) are clinically classified into stage III or stage IV based upon extent of spread of metastatic disease. Previous studies, evaluating MUP using a limited sequencing of BRAF, NRAS, and KIT, have shown a similar frequency of mutations as cutaneous samples. Methods: We identified and performed retrospective chart review on 43 patients treated at the University of Colorado who presented with a melanoma of unknown primary. We excluded patient who presented with a preceding pigmented lesion treated with excision or cryotherapy without a histological diagnosis. After informed consent, DNA was extracted from the tumor samples of these 43 patients. Whole exome sequencing (WES) was performed with exome capture on an Illumina HiSeq sequencer. Results: Our cohort showed a male predominance at 58.1%. The median age at diagnosis was 50.6 years. In our cohort, 93% were Caucasian, while 4.7% were Hispanic and 2.3% were of unknown ethnic origin. 9.3% of patient had a family history of melanoma. Sun exposure was documented in 39.5% of patients and its presence was associated with an increased survival (Median OS of 3.7 vs 1.3 years, p = 0.026). Patients with stage III melanoma had an increased survival (Median OS of 6.8 vs 1.3 years, p = 0.013). Genomic analysis showed mutational pattern similar to cutaneous melanoma with 50% harboring a BRAF mutation, 12% with an NRAS mutation, and 19% carrying an NF1 variant. We found mutational signatures for each tumor and classified each against a larger cohort of cutaneous, mucosal and acral melanomas. Conclusions: We present the genomic data of a large cohort of MUP. The mutational profile of MUP is consistent with other cutaneous melanomas.