MTAP loss in anal melanoma: A genomic landscape study.

4 Background: Anal melanoma (AM) is a rare, highly aggressive malignancy with poor prognosis, and thus further exploration of genomic profiling is essential in development of the targeted therapies. Recent evidence has emerged that novel anti-cancer treatments focused on synthetic lethality mechanisms may have efficacy in patients with clinically advanced melanomas. Methods: Using the FoundationOne CDx assay, 211 AM underwent hybrid capture based comprehensive genomic profiling (CGP) to identify all classes of genomic alterations (GA). Microsatellite instability status (MSI) and tumor mutation burden (TMB) were determined from the sequencing data. PD-L1 expression was determined by immunohistochemistry (IHC) using the Dako TPS score (0% = negative; 1-49% = low positive and >50% = high positive). Results: 35 (16.6%) of AM featured whole or partial loss (homozygous deletion) of the MTAP gene. Of the 35 AM with MTAP loss (MTAPloss+), there were 26 cases with 8/8 exons lost, 4 with 7/8 exons lost, 1 with 5/8 exons lost, 2 with 3 exons lost and 2 with 2 exons lost. The AM with MTAPloss+ were slightly younger (median age of 65 vs 68 years) and more often male gender (51.4% vs 39.8%), compared to MTAP wild type type (MTAPloss-), but these differences were not significant. Biomarkers of immunotherapy response including MSI High status (0.0% in both groups) and TMB (median 1.3 vs 2.5 mutations/Mb) were uncommon in both groups. Low level PD-L1 expression was also similar, but more frequent (30.8% vs 34.6%) in both groups. CDKN2A (100.0% vs 28.4%; p