蕈样肉芽肿分子遗传学致病机制的研究进展

Molecular genetic pathogenesis of mycosis fungoides

蕈样肉芽肿是原发皮肤T细胞淋巴瘤中最常见的类型,其发病机制仍然不清楚。研究显示,蕈样肉芽肿存在高频染色体片段拷贝数变异,如染色体7q、1q、17q的扩增和9p21、10q、17p的缺失,导致相应区域上原癌基因扩增和抑癌基因丢失,从而促进肿瘤的发生发展。同时蕈样肉芽肿中存在低频单核苷酸变异,这些变异基因主要集中在细胞周期调控、细胞凋亡、染色质重塑以及T细胞活化相关的通路上。蕈样肉芽肿很少有发生基因融合变异的报道。另外,部分蕈样肉芽肿病例会发生大细胞转化,往往预示疾病进展及药物抵抗等不良预后。总之,蕈样肉芽肿是一种具有高度分子遗传学异质性的复杂疾病,未来还需要更广泛深入的机制研究。

Mycosis fungoides(MF)is the most common subtype of primary cutaneous T-cell lymphoma,and its pathogenesis remains unclear.Recent studies have uncovered high-frequency chromosomal copy number variations in MF,such as gain of chromosomes7q,1q,17q and loss of 9p21,10q,17p,which lead to the gain of proto-oncogenes and loss of tumor suppressor genes,and finally result in tumor development and progression.Moreover,low-frequency single-nucleotide variants have been found in MF,and these mutated genes are mostly enriched in the pathways associated with cell cycle regulation,cell apoptosis,chromatin remodeling as well as T cell activation.Gene-fusion variation is rarely reported in MF.In addition,large cell transformation may occur in some MF cases,and often indicates poor prognoses such as disease progression and drug resistance.In conclusion,MF is a complex disease with highly molecular genetic heterogeneity,and more extensive and intensive researches on its pathogenesis are needed in the future.