SLURP‐1 is mutated in Mal de Meleda, a potential molecular signature for melanoma and a putative squamous lineage tumor suppressor gene

Abstract

Our study underscores cases of Middle Eastern MDM with SLURP1 mutations and skin malignancies at PPK sites. Our findings also highlight a plausible epithelial lineage-specific tumor suppressor role for the SLURP1 gene, as well as a role in the development and metastasis of melanoma and thus a potential molecular signature for melanoma.

Amelanotic melanoma arising in an area of SLURP‐1 mutated Mal de Meleda

“…To date, up to 17 different mutations of the SLURP‐1 gene have been described in relation to MDM phenotypes . The c.82delT mutation, found in our patient, was previously reported in several ethnicities with high rates of consanguinity (Tunisian, Algerian, Italian, Scottish, and Croatian) and seems to be the most common mutation in the Mediterranean population indicating a founder effect of Mediterranean origins . Melanoma can arise during hereditary PPK (Papillon–Lefevre syndrome, Nagashima‐type palmoplantar keratosis, Greither's disease) .…”

“…Melanoma can arise during hereditary PPK (Papillon–Lefevre syndrome, Nagashima‐type palmoplantar keratosis, Greither's disease) . Melanoma has been reported as the predominant cutaneous malignancy occurring in the hyperkeratosis area in patients with MDM . To the best of our knowledge, nine cases of melanoma associated with MDM have been previously reported .…”

“…Melanoma has been reported as the predominant cutaneous malignancy occurring in the hyperkeratosis area in patients with MDM . To the best of our knowledge, nine cases of melanoma associated with MDM have been previously reported . These cases share some common characteristics: origin on lesional skin, the location on the upper extremities, and high Breslow index (BI).…”

“…The increased incidence of melanoma in MDM patients is, in part, related to the lack of proapoptotic effect of SLURP‐1 as well as to the impaired T‐cell activation and tumor monitoring with a significant role of prolonged inflammation in hyperkeratotic skin . A recent study demonstrated that SLURP‐1 may function as a squamous lineage‐specific tumor suppressor gene and melanocytic‐derived tumors . High BI may be explained by the occurrence of tumors on a previous chronic skin condition responsible for diagnosis delays.…”

“…Mal de Meleda (MDM) is an autosomal recessive palmoplantar erythrokeratoderma caused by homozygous mutations of the SLURP‐1 gene . Cutaneous malignancies have been unusually found on palmoplantar keratoderma (PPK) sites . We report a new case of an achromic acral melanoma developing on a hyperkeratotic area on the ankle of a patient with MDM.…”