Targetable mutations in cutaneous skin cancers: A comparative study across melanoma, squamous cell carcinoma, basal cell carcinoma, and Merkel cell carcinoma.

Abstract

e21555 Background: Skin cancers, including melanoma, squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and Merkel cell carcinoma (MCC), exhibit unique clinical and molecular characteristics. The prevalence of targetable genomic alterations (TGAs) may influence treatment strategies. This retrospective study compared the frequency and types of targetable mutations among these subtypes. Methods: A retrospective analysis was conducted on 50 patients diagnosed with cutaneous skin cancer, including 28 with melanoma, 13 with SCC, 5 with BCC, and 4 with MCC. The study began with 80 patients, excluding 29 for missing data and 1 for being categorized under multiple cancer types. We conducted a descriptive analysis using GraphPad Prism Software, where mutations were evaluated as continuous variables. The statistical significance of differences between groups was assessed using the Kruskal-Wallis test, given the non-normal distribution of data. Pairwise comparisons between groups were also performed. The median number of targetable mutations, race, age, sex, survival status, and the most common mutations in each subtype were analyzed. Data was sourced from Signatera™ assay database to obtain the primary endpoints. Marker values were treated as continuous variables in these analyses. All analyses were executed in GraphPad Prism software. Results: No significant differences were observed in age (p = 0.31), sex (p = 0.09), or survival status (p = 1) among subgroups. The median number of targetable mutations was 2.25 (IQR = 3) in melanoma, 3.7 (IQR = 4) in SCC, 2.3 (IQR = 2) in BCC, and 6.85 (IQR = 6.75) in MCC; however, these values did not differ significantly (p = 0.31). Melanoma presented the highest number of unique mutations (n = 34), followed by SCC (30), BCC (14), and MCC (11). In melanoma, the most frequent mutations involved BRAF (n = 17), TP53 (n = 7), and CDKN2A (n = 8). SCC was dominated by TP53 (n = 13), while BCC featured TP53 (n = 6), PTCH1 (n = 2), and ASXL1 (n = 2). MCC was characterized by RB1 (n = 2) and EGFR (n = 2). Despite these subtype-specific patterns, the overall prevalence of targetable mutations did not differ significantly among the four groups. Conclusions: No significant differences were observed in the number of targetable mutations among melanoma, SCC, BCC, and MCC. Although melanoma showed the highest number of unique mutations (dominated by BRAF and TP53) and SCC had a high frequency of TP53, these patterns were not statistically significant. These findings suggest that targetable mutations may be similarly prevalent across subtypes, underscoring the need for larger studies to clarify their clinical significance and inform targeted therapy.