Neurofibromatosis type 1 (NF1) predisposes to a spectrum of peripheral nerve sheath tumors, ranging from benign plexiform neurofibromas (PN) to atypical neurofibromatous neoplasms of uncertain biological potential (ANNUBP) and malignant peripheral nerve sheath tumors (MPNST). Tumorigenesis follows a multistep molecular cascade initiated by biallelicNF1inactivation, followed byCDKN2Aloss and disruption of the Polycomb Repressive Complex 2 (PRC2). These events guide chromatin remodeling, widespread epigenetic dysregulation, and activation of oncogenic pathways such as RAS/MAPK and PI3K/AKT. Here, we integrate genomic, transcriptomic, and epigenomic studies to delineate the molecular trajectories underlying tumor progression and to define promising biomarkers for the early detection of malignant transformation. Emerging liquid biopsy approaches, based on circulating tumor DNA (ctDNA) analyses, reveal distinctive copy number variations (CNVs) and methylation patterns that mirror tissue-derived profiles, enabling the detection of malignant transformation. Together, these findings support a model in which cumulative genetic and epigenetic alterations drive the PN–ANNUBP–MPNST continuum. They also underscore the value of multi-omics and liquid biopsy-based strategies to improve early diagnosis, patient risk stratification, and personalized management of NF1-associated tumors, thereby advancing precision medicine in this complex disease spectrum.
1型神经纤维瘤病（NF1）易引发一系列外周神经鞘肿瘤，其谱系包括良性丛状神经纤维瘤（PN）、生物学潜能不确定的非典型神经纤维瘤性肿瘤（ANNUBP）以及恶性外周神经鞘肿瘤（MPNST）。肿瘤发生遵循多步骤分子级联反应：起始于NF1双等位基因失活，随后发生CDKN2A缺失及多梳抑制复合物2（PRC2）功能破坏。这些事件共同驱动染色质重塑、广泛的表观遗传失调以及RAS/MAPK和PI3K/AKT等致癌通路的激活。本文整合基因组学、转录组学与表观基因组学研究，系统阐释肿瘤进展的分子轨迹，并确立用于早期检测恶性转化的潜在生物标志物。基于循环肿瘤DNA（ctDNA）分析的新型液体活检方法，可检测到与组织样本特征一致的拷贝数变异（CNV）和甲基化模式，从而实现恶性转化的早期识别。这些发现共同支持一个模型：累积的遗传与表观遗传改变驱动着PN–ANNUBP–MPNST的连续演进过程。同时，研究结果凸显了多组学与液体活检策略在改善NF1相关肿瘤的早期诊断、患者风险分层及个体化管理方面的重要价值，从而推动这一复杂疾病谱系的精准医疗发展。
肿瘤(癌症)患者之家