Abstract
552 Background: mPSCC is an aggressive malignancy with limited treatment options. Using CGP, we compared the therapy impacting genomic alterations (GA) between mPSCC and cutaneous mCSCC. Methods: DNA was extracted from 40 microns of FFPE samples from 78 cases of mPSCC and 338mCSCC.Comprehensive genomic profiling (CGP) was performed using a hybrid-capture, adaptor ligation based next generation sequencing assayto a mean coverage depth of > 500X. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. Results: mPSCC patients were younger than mCSCC (Table). Both tumors types feature high CDKN2A, TERT and FAT1 GA frequencies. NOTCH1 and PTCH1 GA are also more common in mCSCC than mPSCC. CD274 ( PD-L1) amplification was rare in both tumor types. Targeted therapy opportunities in mPSCC included alterations in kinase pathways ( EGFR GA in 6%; FGFR3 and ERBB2 GA in 4%); MTOR pathway ( NF1 GA in 7% and PTENGA in4%) and DNA repair pathway ( BRCA2and ATMGA in 7%). TMB was significantly higher in the UV light exposed mSCC than mPSCC with both tumor types having potential for responsiveness to immunotherapies. MSI-High status was extremely rare for both mPSCC and mCSCC. HPV viral DNA was identified in 29% on mPSCC but only in 5% of mCSCC. TP53 GA were significantly more frequent in HPV- than HPV+ mPSCC and mCSCC respectively (P < 0.0001 for both). Clinical outcomes of selected patients will be presented. Conclusions: mPSCC is a unique subtype of SCC with distinctive genomic features that contrast with those identified in mCSCC of non-penile UV light exposed skin. Given the potential opportunities for targeted therapies and immunotherapies that can be uncovered, continued study of CGP for the guidance of treatment for patients with mPSCC appears warranted.[Table: see text]
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