Track: Basic Science

Topic: Neoplasia,Carcinogensis,Tumor Biology

Abstract:

Marjolin’s ulcer is an aggressive form of cutaneous squamous cell carcinoma (muSCC) that arises in chronically inflamed wounds. Correspondingly, one major form of vulvar squamous cell carcinoma (vSCC) is often associated with lichen sclerosus or inflammatory lesions in postmenopausal women and does not harbor detectable HPV infection. We sought to assess the genomics of a cohort of muSCCs, and compare the genomics to our large series of HPV(–) vSCCs, with an aim to identify similar or distinct mutational signatures. 17 muSCC and 280 vSCC were tested by comprehensive genomic profiling (CGP) by a hybrid capture-based DNA sequencing platform (FoundationOne®CDx). For muSCC, primary site was foot (n=6), gluteal (n=3), leg (n=3), hand (n=2), arm (n=2), breast (n=1); median age was 58 years and 53% were male. No hrHPV sequences or UV signature was identified in any muSCC. In the vSCC cohort, 178/280 did not contain hrHPV sequences. Comparing muSCC and HPV(–) vSCC, the nine most frequently mutated genes were shared: TP53 (59% of muSCC v. 82% of HPV(–) vSCC), TERTp (41% v. 72%), CDKN2A (41% v. 55%), CCND1 (6% v. 23%), FAT1 (18% v. 25%), NOTCH1 (12% v. 19%), PIK3CA (6% v. 16%), EGFR (6% v. 13%), and CASP8 (12% v. 12%). Tumor mutational burden (TMB) was also statistically similar (3.1 vs. 3.8 mut/Mb, p=.26). Overall, muSCC shows similar genomic alterations and TMB to HPV(–) vSCCs. CGP of inflammation-associated SCCs may be important to more fully inform therapeutic options and stratification in clinical trials.

Isabella Raffa

Affiliation

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Marjolin's Ulcer: Comprehensive Genomic Profiling Reveals Potentially Actionable Biomarkers and Mutational Similarity to HPV(–) Vulvar Squamous Cell Carcinoma