Primary central nervous system melanoma is rare and characterized by a variable prognosis, and no current treatment guidelines exist. We describe the clinical course of a 70-year-old female patient diagnosed with primary leptomeningeal melanoma (LMN) whose case represents the diagnostic and management challenges of this tumor. Targeted genomic sequencing of 315 genes from this tumor revealed GNAQ Q209L mutation and low (4 mutations/Megabase) tumor mutation burden (TMB). Wild-type NRAS, KIT, and BRAF were also observed. A cohort of 4,787 melanomas was subsequently analyzed to identify additional primary central nervous system melanomas, of which 10 additional tumors met pathologic criteria (0.21% of total melanoma cohort). These tumors were genomically assessed according to the same targeted sequencing panel, and 6 of the tumors were also found to harbor a GNAQ mutation. All 10 tumors had low (less than or equal to 2 mutations/Megabase) TMB indicating a potential trend between G-protein-coupled receptor (GPCR) alterations and low TMB in LMNs. GPCR alterations were found to significantly correlate with TMB across the cohort of 4,787 melanomas, supporting this potential finding in the limited LMN subset.

中文翻译：

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基因组分析揭示了低的肿瘤突变负担，这可能与一系列原发性脑膜脑黑素瘤中的GNAQ / 11改变有关。

原发性中枢神经系统黑色素瘤很少见，预后可变，目前尚无治疗指南。我们描述了一名诊断为原发性脑膜脑黑素瘤（LMN）的70岁女性患者的临床病历，该病例代表了该肿瘤的诊断和管理挑战。该肿瘤中315个基因的靶向基因组测序显示出GNAQ Q209L突变和低（4个突变/ Megabase）肿瘤突变负担（TMB）。还观察到了野生型NRAS，KIT和BRAF。随后分析了一组4,787例黑色素瘤，以识别其他原发性中枢神经系统黑色素瘤，其中有10例符合病理标准的肿瘤（占总黑色素瘤队列的0.21％）。根据相同的靶向测序小组对这些肿瘤进行了基因组评估，还发现其中的6个肿瘤带有GNAQ突变。所有10个肿瘤的TMB均较低（小于或等于2个突变/ Megabase），表明L蛋白中G蛋白偶联受体（GPCR）改变与TMB较低之间存在潜在趋势。在整个4,787个黑色素瘤队列中，发现GPCR改变与TMB显着相关，从而支持了在有限的LMN亚组中的这一潜在发现。