Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2017 Apr 11;116(8):990-993.
doi: 10.1038/bjc.2017.49. Epub 2017 Mar 2.

MEK inhibition appears to improve symptom control in primary NRAS-driven CNS melanoma in children

Veronica A Kinsler  1   2 , Patricia O'Hare  3 , Thomas Jacques  4 , Darren Hargrave  3   5 , Olga Slater  3
Affiliations
Case Reports

MEK inhibition appears to improve symptom control in primary NRAS-driven CNS melanoma in children

Veronica A Kinsler et al. Br J Cancer. .

Abstract

Background: Primary melanoma of the CNS in children is extremely rare, and usually linked to congenital melanocytic naevus syndrome, caused by mosaicism for oncogenic NRAS mutations. Outcome is fatal in all cases. Data from murine and in vitro studies suggest that MEK inhibition is a possible therapeutic option.

Methods: Four children with NRAS-mutated CNS melanoma were treated with Trametinib on a compassionate basis.

Results: All four had an improvement in symptoms and objectively in signs. These varied from mild improvement for 1 month, to a sustained symptom-free period of 9 months in one case. In all cases there was eventual disease progression through treatment, followed by rapid death after discontinuation. There were no clinically-significant side effects.

Conclusions: Trametinib is the first therapy to show any objective or measurable effect in NRAS-mutated primary CNS melanoma, with few side effects in this small series. The role of this therapy should be explored further in this rare paediatric tumour.

PubMed Disclaimer

Conflict of interest statement

DH has acted as an unpaid advisor for Novartis. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Examples of phenotype in congenital melanocytic naevus syndrome.Written consent was obtained for clinical photo publication. (A) Example of severe cutaneous phenotype. (B) Diffuse melanotic leptomeningeal disease—this requires biopsy and both histological and genetic testing before malignancy can be established, and should be viewed in the context of the baseline screening MRI of the CNS under 1 year. This case was leptomeningeal melanoma.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Acosta FL Jr., Binder DK, Barkovich AJ, Frieden IJ, Gupta N (2005) Neurocutaneous melanosis presenting with hydrocephalus. Case report and review of the literature. J Neurosurg 102(1 Suppl): 96–100. - PubMed
    1. Barkovich AJ, Frieden IJ, Williams ML (1994) MR of neurocutaneous melanosis. AJNR Am J Neuroradiol 15(5): 859–867. - PMC - PubMed
    1. Bastian BC, Olshen AB, LeBoit PE, Pinkel D (2003) Classifying melanocytic tumors based on DNA copy number changes. Am J Pathol 163(5): 1765–1770. - PMC - PubMed
    1. CRUK (2016) Cancer Research UK statistics Available at: http://www.cancerresearchuk.org/health-professional/cancer-statistics.
    1. Dechaphunkul A, Kayasut K, Oearsakul T, Koonlaboon K, Sunpaweravong P (2011) Common presentation in an uncommon disease: case report of a patient with primary diffuse leptomeningeal melanocytosis. J Clin Oncol 29(33): e816–e818. - PubMed

Publication types

MeSH terms