Scripps Translational Science Institute, The Scripps Research Institute, La Jolla, California.
Department of Internal Medicine, Scripps Clinic/Scripps Green Hospital, La Jolla, California.
Pigment Cell Melanoma Res. 2020 May;33(3):458-465. doi: 10.1111/pcmr.12839. Epub 2019 Dec 18.
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.
原发性中枢神经系统黑色素瘤较为罕见，其预后多变，目前尚无治疗指南。我们描述了一名 70 岁女性患者的临床病程，该患者被诊断为原发性软脑膜黑色素瘤（LMN），其病例代表了该肿瘤的诊断和治疗挑战。对该肿瘤的 315 个基因进行靶向基因组测序显示 GNAQ Q209L 突变和低（4 个突变/Megabase）肿瘤突变负担（TMB）。还观察到野生型 NRAS、KIT 和 BRAF。随后对 4787 例黑色素瘤进行了分析，以确定其他原发性中枢神经系统黑色素瘤，其中另外 10 例肿瘤符合病理标准（总黑色素瘤队列的 0.21%）。根据相同的靶向测序面板对这些肿瘤进行了基因组评估，其中 6 个肿瘤也发现存在 GNAQ 突变。所有 10 个肿瘤的 TMB 均较低（小于或等于 2 个突变/Megabase），这表明在 LMN 中 G 蛋白偶联受体（GPCR）改变和低 TMB 之间可能存在趋势。在 4787 例黑色素瘤的队列中发现 GPCR 改变与 TMB 显著相关，这支持了在有限的 LMN 亚组中的这一潜在发现。
