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• W2912609892 abstract "551 Background: Anal melanomas (AM) share histologic features with cutaneous melanomas (CM), are highly aggressive and behave in a distinct clinicopathologic pattern. We performed comprehensive genomic profiling (CGP) of AM to learn of potential matched targeted and immunotherapies that may improve clinical outcomes for the disease. Methods: FFPE tissues from late stage AM (81 cases) and CM (1804 cases) underwent hybrid-capture based CGP to evaluate all classes of genomic alterations (GA). Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. Results: AM and CM had a similar age, but AM females and CM males were significantly more common (P < 0.0001) (Table). Given the UV light exposure in the CM, the GA/tumor was significantly higher than AM as were the median TMB and frequency of TMB ≥ 10 and 20 mutations/Mb (P < 0.0001 for all comparisons). All AM and CM were MS-stable. The contrast in S FB1 mutations in AM and TERT GA in CM were significant (P < 0.0001). AM featured significantly more KIT GA than CM (P < 0.0001), whereas CM featured significantly more BRAF GA (P < 0.0001). Only 11% of AM BRAF GA were V600E whereas 74% of CM BRAF GA were V600E (P < 0.0001). MTOR pathway targets including NF1 and PTEN were commonly altered in both tumor types. Potentially targetable PDGFRA and ERBB2 GA were found in AM but not in CM. Conclusions: UV light exposure drives high GA/tumor and TMB in CM, both associated with immune checkpoint inhibitor (ICPI) responsiveness, whereas AM lacks the high TMB and therefore is far less likely to benefit from ICPI treatments. CM is classically associated with opportunities for anti-BRAF therapies and AM with an array of kinase targets including KIT, BRAF, PDGFRA and ERBB2. Finally, MTOR pathway targets are common to both tumor types. [Table: see text]" @default.
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• W2912609892 date "2019-02-01" @default.
• W2912609892 modified "2023-09-27" @default.
• W2912609892 title "Anal melanoma: A comparative comprehensive genomic profiling study." @default.
• W2912609892 doi "https://doi.org/10.1200/jco.2019.37.4_suppl.551" @default.
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