Patel Sapna P, Kim Dae Won, Lacey Carol L, Hwu Patrick
From the Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Medicine (Baltimore). 2016 Jan;95(4):e2336. doi: 10.1097/MD.0000000000002336.
The rapid advances in the molecular biology and genetics have improved the understanding of molecular pathogenesis of v-Raf murine sarcoma viral oncogene homolog B (BRAF), feline sarcoma viral oncogene v-kit (KIT), and neuroblastoma v-Ras oncogene homolog (NRAS) mutant melanomas with the subsequent development of targeted therapeutic agents. However, only limited data are available for melanoma harboring other somatic than BRAF, KIT, and NRAS mutations. Mutations in guanine nucleotide-binding protein Q polypeptide (GNAQ) and guanine nucleotide-binding protein alpha-11 (GNA11), alpha subunits of heterotrimeric G proteins, constitutively activate mitogen-activated protein kinase (MAPK) pathway in uveal melanoma. However, there are no reports of GNA11 mutations in cutaneous melanomas. A 48-year-old woman was diagnosed with cutaneous nodular melanoma on the left scalp. Mutation analysis of the tumor revealed a GNA11 Q209L mutation. There was no evidence of uveal melanoma or malignant blue nevus in ophthalmologic exam, imaging studies, and pathology review. To our knowledge, this is the first case report to demonstrate cutaneous origin melanoma harboring a GNA11 Q209L mutation.
分子生物学和遗传学的快速发展增进了人们对携带v-Raf鼠肉瘤病毒癌基因同源物B(BRAF)、猫肉瘤病毒癌基因v-kit(KIT)和神经母细胞瘤v-Ras癌基因同源物(NRAS)突变的黑色素瘤分子发病机制的理解,随后靶向治疗药物也得以开发。然而,对于携带BRAF、KIT和NRAS以外其他体细胞突变的黑色素瘤,仅有有限的数据。鸟嘌呤核苷酸结合蛋白Q多肽(GNAQ)和鸟嘌呤核苷酸结合蛋白α-11(GNA11)(异源三聚体G蛋白的α亚基)的突变可在葡萄膜黑色素瘤中持续激活丝裂原活化蛋白激酶(MAPK)途径。然而,尚无皮肤黑色素瘤中存在GNA11突变的报道。一名48岁女性被诊断为左侧头皮皮肤结节性黑色素瘤。对肿瘤的突变分析显示存在GNA11 Q209L突变。眼科检查、影像学研究及病理检查均未发现葡萄膜黑色素瘤或恶性蓝痣的证据。据我们所知,这是首例证实携带GNA11 Q209L突变的皮肤源性黑色素瘤的病例报告。