Primary melanoma of the CNS in children is driven by congenital expression of oncogenic NRAS in melanocytes
Menée à l'aide d'un modèle murin et sur des échantillons tumoraux prélevés sur deux patients pédiatriques atteints d'un mélanome primitif du système nerveux central, cette étude suggère que l'acquisition de mutations somatiques du gène NRAS dans les mélanocytes du système nerveux central prédispose les enfants, et non les adultes, à cette maladie
NRAS mutations are common in human melanoma. To produce a mouse model of NRAS-driven melanoma, we expressed oncogenic NRAS (NRASG12D) in mouse melanocytes. When NRASG12D was expressed in the melanocytes of developing embryos, it induced melanocyte proliferation and congenital melanocytic lesions reminiscent of human blue nevi, but did not induce cutaneous melanoma. Unexpectedly however, it did induce early onset primary melanoma of the central nervous system (CNS). The tumors were rapidly proliferating and caused neurological symptoms, rapid health deterioration and death. NRAS is not a common driver oncogene of primary melanoma of the CNS in adults, but we report two cases of primary melanoma of the CNS in children, both of which carried oncogenic mutations in NRAS. We conclude that acquisition of somatic mutations in NRAS in CNS melanocytes is a predisposing risk factor to primary melanoma of the CNS in children and present a mouse model of this disease.