Experimental treatment of NRAS-mutated neurocutaneous melanocytosis with MEK162, a MEK-inhibitor

Heidi V.N. Küsters-Vandevelde, Annelieke E.C.A.B. Willemsen, Patricia J.T.A. Groenen, Benno Küsters, Martin Lammens, Pieter Wesseling, Melika Djafarihamedani, Jos Rijntjes, Hans Delye, Michel A. Willemsen, Carla M.L. van Herpen, Willeke A.M. Blokx

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

43 Citaten (Scopus)


Neurocutaneous melanosis (NCM) is a rare congenital disorder characterized by the association of large and/or multiple congenital melanocytic nevi (CMN) of the skin with melanocytic lesions of the leptomeninges, including melanocytosis. Leptomeningeal melanocytosis carries a poor prognosis once neurological symptoms develop. Despite surgery, which is often not radical, few other treatment options exist. Recently, it was demonstrated that early embryonic, post-zygotic somatic mutations in the NRAS gene are implicated in the pathogenesis of NCM. In this report, we present a 13-year-old boy with NCM and progressive symptomatic leptomeningeal melanocytosis. A somatic NRASQ61K mutation was present in both CMN as well as the melanocytosis. Despite repeated surgery, the patient showed clinical progression. Therefore, treatment with MEK162, a MEK inhibitor, was started on compassionate use base. The patient died only five days later, i.e. too early to expect a clinical effect of MEK162 therapy. We therefore studied the effect of MEK162 at the protein level in the leptomeningeal tumor by immunohistochemical and Western Blot analyses using Ki67 and pERK antibodies. We observed lower MIB-1 expression and lower pERK expression in the post-treatment samples compared to pre-treatment, suggesting a potential effect of MEK inhibiting therapy. Further studies are needed to determine whether MEK inhibitors can effectively target NRAS-mutated symptomatic NCM, a rare but potentially fatal disease.

Originele taal-2Engels
TijdschriftActa neuropathologica communications
Nummer van het tijdschrift1
StatusGepubliceerd - 27 jan. 2014
Extern gepubliceerdJa


Duik in de onderzoeksthema's van 'Experimental treatment of NRAS-mutated neurocutaneous melanocytosis with MEK162, a MEK-inhibitor'. Samen vormen ze een unieke vingerafdruk.

Citeer dit