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• W4212779236 abstract "4 Background: Penile squamous cell carcinoma (SCC) is a rare and aggressive malignancy with few treatments in the advanced setting and little success of immune-checkpoint inhibitions (ICI). Around half of penile SCC cases are linked to HPV infection. We aimed to report the landscape of somatic alterations and ICI-related biomarkers in penile SCC in the Caris Life Sciences dataset and to establish signatures for HPV-dependent and HPV-independent oncogenesis. Methods: Penile SCC tumors were analyzed using next-generation sequencing of DNA (TruSeq, 45 genes; NextSeq, 592 genes and NovaSeq, whole exome sequencing (WES)) and RNA (NovaSeq). PD-L1 expression was tested by IHC using SP142. Microsatellite instability (MSI) was tested by fragment analysis, IHC and NGS. Tumor mutational burden (TMB) was measured by counting all somatic mutations found per tumor (TMB-high: >10 mutations per MB). HPV16/18 status was determined using WES when available. Significance was determined using chi-square and Wilcoxon rank sum test and adjusted for multiple comparisons (q-value <0.05). Results: Among the entire cohort (N=108), the median age was 66 years and 79.6% of tumors were primary and 20.4% of tumors were metastatic. In the overall cohort, the most frequently detected mutations were TP53 (46%), CKDN2A (26%), PIK3CA (25%), TERT promoter (22%), KMT2C (16%) and NOTCH1 (14%), consistent with previous reports. Overall, 51% of tumors were PD-L1+ (SP142, >1%), 10.7% had high TMB, and 1.1% had dMMR/MSI-H. Of the 108 tumors, 29 had HPV status tested by WES (HPV16/18+, n=13 and HPV16/18-, n=16). KMT2C mutations (33% vs 0%) and FGF3 amplifications (30.8% vs 0%) were specific to HPV16/18+ tumors, while CDKN2A mutations (37.5% vs 0%) were exclusive to HPV16/18- tumors. HPV16/18+ tumors also had a trend towards decreased TP53 (7.7% vs 63%) and TERT promoter (25% vs 77%) alterations (Table). TMB-high were exclusively found in the HPV16/18+ group (30.8% vs 0%), while PD-L1 and dMMR/MSI-H status were comparable between the two groups. Conclusions: To our knowledge, our comprehensive NGS study of penile SCC somatic alterations is the largest to date. HPV16/18+ vs HPV16/18- penile SCC were molecularly distinct tumors, consistent with previous reports. Our finding that TMB-high was exclusive to patients with HPV16/18+ tumors requires confirmation in larger datasets and could be used for better patient stratification in ICI clinical trials.[Table: see text]" @default.
• W4212779236 created "2022-02-24" @default.
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• W4212779236 date "2022-02-20" @default.
• W4212779236 modified "2023-10-03" @default.
• W4212779236 title "Comprehensive genomic profiling of penile squamous cell carcinoma and impact of HPV status on immune-checkpoint inhibition-related biomarkers." @default.
• W4212779236 doi "https://doi.org/10.1200/jco.2022.40.6_suppl.004" @default.
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