Comparative genomic profiling (CGP) of refractory/metastatic penile (mPSCC) and non-penile cutaneous squamous cell carcinoma (mCSCC).

552Background: 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 pathwa...