Etiology of Congenital Melanocytic Nevi and Related Conditions

The Dual PI3K/mToR Inhibitor Omipalisib/GSK2126458 Inhibits Clonogenic Growth in Oncogenically-transformed Cells from Neurocutaneous Melanocytosis

“…Cell culture, cytotoxicity, viability and clonogenicity assays. Culture of clonogenic cells from NCM patients' lesions and nevosphere colony formation has been described by us in detail previously (1). Clonogenicity was estimated by measuring colony formation on Geltrex ® matrix (ThermoFisher Scientific, Waltham, MA, USA cat.…”

“…Neurocutaneous melanocytosis (NCM) is a congenital neoplastic disease characterized by melanocytic proliferations in the brain and skin (1). Although patients with asymptomatic NCM may live without much problems for extended periods, the onset of symptoms in NCM generally indicates the beginning of an aggressive clinical course, with a poor prognosis and frequently death occurring within 2-3 years of diagnosis (2).…”

Pericyte ontogeny: the use of chimeras to track a cell lineage of diverse germ line origins

“…Their localization within blood vessels of murine forebrain meninges [93] and the heart [95] in sites shown by chick-quail chimeras to harbor NCC may reflect either a normal but as-yet unidentified secretory function of pigment cells, or simply a sensitized response to signals deployed for pericytic recruitment and vascular stabilization. In favor of the former, leptomeningeal melanocytosis is a hallmark of lethal neurological symptoms in syndromic forms of the rare giant congenital melanocytic nevus [96,97] and primary pediatric melanoma often occurs in the meninges [98][99][100].…”

Histone deacetylase inhibitor Vorinostat (SAHA) suppresses micropthalmia transcription factor expression and induces cell death in nevocytes from large/giant congenital melanocytic nevi

“…L/GCMN and associated neurocutaneous melanocytosis (NCM) are considered a dysgenetic/neoplastic neurocristopathy [9] with a high risk of malignant transformation [10]. L/GCMN are characterized by pigmented lesions covering large areas of skin, with a projected adult size of at least 20 cm or more [11], presenting at birth or appearing shortly thereafter [12]. Current treatment modalities for L/GCMN patients are mostly surgical, with potential for disfigurement, residual scar deformity, residual nevus in areas of the body where the risk of functional disturbance outweighs the benefit of excision and psychological trauma from multiple surgeries.…”