capture-based CGP to evaluate all classes of genomic alterations (GAs). Tumor mutational burden (TMB) was determined on up to 1.1 Mb of sequenced DNA and microsatellite instability (MSI) was determined on up to 114 loci. PD-L1 expression was determined by IHC (Dako 22C3).RESULTS: Median ages were similar except crvSCC, which were younger (Table ). GA/tumor were similar. HPV-16/18 detection was lowest in furthSCC and vulSCC and highest in manSCC, fanSCC and crvSCC. TP53 GA were inversely associated with HPV status. PIK3CA GA ranged from 22% to 43% in all groups. DDR GA (BRCA1/2, ATM, others) were low (<1-3%) throughout. Cell cycle GA were most frequent in external cases (penSCC, furthSCC, vulSCC). MTOR pathway GA (PTEN, FBXW7) were most frequent targeted therapy options. RTK options were 1% in BRAF/ERBB2 but FGFR3 targets present in >5% of murthSCC, manSCC, crvSCC and fanSCC. NOTCH1 GA were present in >15% in penSCC and vulvSCC. MSIhigh status was present in only 0-1%. TMB >10 mut/MB was >15% in manSCC, fanSCC and crvSCC. CD274 amplification was significantly increased (>4%) in penSCC, vulSCC, crvSCC and fanSCC. PD-L1 low expression was >25% in all pSCC except crvSCC and high expression was >18% in all pSCC except urthSCC and manSCC.CONCLUSIONS: Despite similar histology, pSCC differ widely in GA and HPV status. PIK3CA is the most frequent targeted therapy opportunity followed by MTOR pathway and cell cycle with RTK targets extremely rare. PARP inhibitor options appear low given the infrequent finding of DDR GA. However, immune checkpoint inhibitor options are frequently identified as evidenced by TMB>10 mut/MB, relatively frequent CD274 amplification and frequent PD-L1 expression data.
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