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Mutational landscape in squamous cell carcinoma of the nail unit
Emi Dika1,2, Dario de Biase3, Martina Lambertini1,2
1Dermatology, IRCCS di Policlinico Sant'Orsola, Bologna, Italy.
Abstract:
Squamous cell carcinoma (SCC) is the most common malignancy of the nail unit. Pathogenetic mechanisms are yet to be determined, and a deeper molecular characterization of this disease is still necessary. The aim was to obtain a molecular characterization of NU SCC samples using an NGS approach to identify the genetic drivers involved in this tumor. The presence of HPV infection was also assessed. Furthermore, the mutational status was correlated with specific clinical-pathological features for a better insight into the carcinogenesis of this uncommon tumor. We analysed twenty paraffin-embedded nail unit SCC samples from patients diagnosed with primary SCC of the nail unit by next genome sequencing. In the 20 tested samples, the neoplastic cells enrichment ranged from 10% to 50% (mean value: 25.7%). In 14/20 cases (70.0%), at least one mutation was detected; whereas in the other six cases (30.0%), no alterations were observed ('wild-type/WT cases'). Overall, a total of 23 mutations were identified in the 20 specimens. TP53 was the most mutated gene (6/20 cases, 30.0%), while cKit, GNAS, EGFR, DICER1 and CTNNB1 were observed in one sample each (5.0%). No clinical-pathological parameters (age, sex, depth of invasion-DOI, histological subtype, grading and HPV) were significantly associated with the mutational status. The nail unit SCC mutational landscape appeared to be heterogeneous, favouring the hypothesis of a complex pathogenesis and an interaction of multiple elements, including HPV infections. This wealth of information undoubtedly improves our understanding of SCC biology.
Insights
Squamous cell carcinoma (SCC) of the nail unit shows a heterogeneous mutational landscape, with TP53 being the most frequently altered gene. This study highlights complex carcinogenesis involving multiple factors, including HPV infection.
Area of Science:
- Oncology
- Genetics
- Dermatology
Background:
- Squamous cell carcinoma (SCC) is the most common nail unit malignancy.
- The molecular basis and pathogenetic mechanisms of nail unit SCC remain largely undetermined.
- A deeper molecular characterization is crucial for understanding this uncommon tumor.
Purpose of the Study:
- To perform molecular characterization of nail unit SCC samples using next-generation sequencing (NGS).
- To identify genetic drivers and assess Human Papillomavirus (HPV) infection in nail unit SCC.
- To correlate mutational status with clinical-pathological features for insights into carcinogenesis.
Main Methods:
- Analysis of twenty paraffin-embedded nail unit SCC samples.
- Next-generation sequencing (NGS) approach for molecular profiling.
- Assessment of HPV infection and correlation with clinical-pathological parameters.
Main Results:
- Mutations were detected in 70% of samples (14/20), with a total of 23 mutations identified.
- TP53 was the most frequently mutated gene (30.0%), followed by cKit, GNAS, EGFR, DICER1, and CTNNB1 (5.0% each).
- No significant association was found between mutational status and clinical-pathological parameters, including HPV status.
Conclusions:
- The nail unit SCC mutational landscape is heterogeneous, suggesting a complex pathogenesis.
- Multiple interacting factors, potentially including HPV infections, contribute to SCC development in the nail unit.
- This molecular data enhances the understanding of SCC biology and carcinogenesis.
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