Rare-43. search for druggable targets in primary nervous system melanotic tumors: melanocytomas, melanotic schwannomas, primary melanomas

Due to the extreme rarity of primary nervous system melanotic tumors, relatively limited studies have been conducted attempting to identify distinguishing mutations and/or druggable targets. Melanocytomas share GNAQ mutations with uveal melanoma (Brain Pathol. 25:202-8, 2015; Acta Neuropathol 119:317-323, 2010); clinical trials in uveal melanomas have shown that MEK inhibition may result in clinical benefit in tumors with these mutations. BRAF V600E mutations (paralleled by BRAF VE1 immunohistochemistry) are targetable by vemurafenib, but large numbers of primary nervous system melanomas have not been assessed. Adding to the problem is the difficulty in pathologically distinguishing these primary melanocytic tumors from each other, or predicting prognosis. Database search for all primary nervous system melanotic tumors seen since 2002 at our institution identified 12 patients, ages 15 months- 64 years, male (8): female (4), encompassing 3 melanocytomas, 1 melanocytoma with focal transformation to melanoma, 3 melanotic schwannomas, 1 malignant melanotic schwannoma, and 4 primary malignant melanomas. All 5 histologically-malignant examples have succumbed, although all melanocytomas are known to be alive, including one with focal melanoma transformation. All were assessed by BRAF VE1 and/or a 26 gene Next Generation Sequencing (NGS) Panel (including GNAQ, NRAS, BRAF, KIT, MAP2K1). Although these methods postdated the date of diagnosis in 10 of 12 patients and therefore...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: RARE TUMORS Source Type: research