2nd Department of Pathology, Semmelweis University, 1191 Budapest, Hungary.
Department of Surgical and Molecular Pathology and the National Tumor Biology Laboratory, National Institute of Oncology, 1122 Budapest, Hungary.
Int J Mol Sci. 2022 May 11;23(10):5384. doi: 10.3390/ijms23105384.
Similar to other malignancies, TCGA network efforts identified the detailed genomic picture of skin melanoma, laying down the basis of molecular classification. On the other hand, genome-wide association studies discovered the genetic background of the hereditary melanomas and the susceptibility genes. These genetic studies helped to fine-tune the differential diagnostics of malignant melanocytic lesions, using either FISH tests or the myPath gene expression signature. Although the original genomic studies on skin melanoma were mostly based on primary tumors, data started to accumulate on the genetic diversity of the progressing disease. The prognostication of skin melanoma is still based on staging but can be completed with gene expression analysis (DecisionDx). Meanwhile, this genetic knowledge base of skin melanoma did not turn to the expected wide array of target therapies, except the BRAF inhibitors. The major breakthrough of melanoma therapy was the introduction of immune checkpoint inhibitors, which showed outstanding efficacy in skin melanoma, probably due to their high immunogenicity. Unfortunately, beyond , mutations and tumor mutation burden, no clinically validated predictive markers exist in melanoma, although several promising biomarkers have been described, such as the expression of immune-related genes or mutations in the IFN-signaling pathway. After the initial success of either target or immunotherapies, sooner or later, relapses occur in the majority of patients, due to various induced genetic alterations, the diagnosis of which could be developed to novel predictive genetic markers.
与其他恶性肿瘤类似，TCGA 网络研究确定了皮肤黑色素瘤的详细基因组图谱，为分子分类奠定了基础。另一方面，全基因组关联研究发现了遗传性黑色素瘤和易感基因的遗传背景。这些遗传研究有助于利用 FISH 检测或 myPath 基因表达谱精细调整恶性黑素细胞病变的鉴别诊断。尽管最初的皮肤黑色素瘤基因组研究主要基于原发性肿瘤，但关于进展性疾病遗传多样性的数据开始积累。皮肤黑色素瘤的预后仍然基于分期，但可以通过基因表达分析（DecisionDx）来完成。同时，皮肤黑色素瘤的这种遗传知识库并没有像预期的那样产生广泛的靶向治疗，除了 BRAF 抑制剂。黑色素瘤治疗的重大突破是免疫检查点抑制剂的引入，这些抑制剂在皮肤黑色素瘤中显示出了出色的疗效，这可能是由于其高度的免疫原性。不幸的是，除了 突变和肿瘤突变负荷外，黑色素瘤中不存在经临床验证的预测标志物，尽管已经描述了几种有前途的生物标志物，例如免疫相关基因的表达或 IFN 信号通路中的突变。在靶向或免疫疗法最初取得成功后，大多数患者迟早会因各种诱导的遗传改变而复发，这些改变的诊断可以开发为新的预测性遗传标志物。
