Differences in the Clinical and Molecular Profiles of Subungual Melanoma and Acral Melanoma in Asian Patients

Simple Summary Melanoma is a type of skin cancer that develops from melanocytes (the cells that give the skin its brown color). Subungual melanoma (nail melanoma) is a rare type of malignant melanoma that arises beneath the nails. Subungual melanoma has been categorized as a type of acral melanoma, which occurs on the hands and feet. Using a genetic study, we found that subungual melanoma showed molecular features that were different from those of acral melanoma. Subungal melanoma had a frequently mutated gene, named G protein subunit alpha Q. Patients with subungual melanoma show better survival than patients with acral melanoma. We suggest that subungual melanoma should be considered as a type of melanoma that is separate from acral melanoma. The genetic evaluation of subungual melanoma is important for advanced cancer patients, so that appropriate targeted therapy may be selected.Abstract Subungual melanoma (SUM) is a rare type of malignant melanoma that arises beneath the nails. SUM is categorized as a type of acral melanoma (AM), which occurs on the hands and feet. SUM is an aggressive type of cutaneous melanoma that is most common among Asian patients. Recent studies reveal that SUM and AM might have different molecular characteristics. Treatment of melanoma relies on analysis of both clinical and molecular data. Therefore, the clinical and molecular characteristics of SUM need to be established, especially during metastasis. To define the mutation profiles of SUM and compare them with those of AM, we performed next-generation sequencing of primary and metastatic tumors of SUM and AM patients. Subungual location was a better independent prognostic factor than acral location for better overall survival (p = 0.001). Patients with SUM most commonly had the triple wild-type (75%) driven by GNAQ (58%) and KIT (25%) mutations, whereas patients with AM had BRAF (28.6%) and RAF (14.3%) molecular types of mutations. Single-nucleotide variations (SNVs) were more common in SUM than in AM, whereas copy number alterations (CNAs) were more common metastatic lesions of AM. Metastatic tumors in patients with SUM and AM showed increases in CNAs (43% and 80%, respectively), but not in SNVs. The number of CNAs increased during metastasis. When compared with AM, SUM has distinct clinical and molecular characteristics.