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Abstract：
Giant cell tumor (GCT) is a bone-destructive benign neoplasm characterized by distinctive multinucleated osteoclast-like giant cells with osteolytic properties distributed among neoplastic stromal cells. GCT is locally aggressive with progressive invasion of adjacent tissues and occasionally displays malignant characteristics including lung metastasis. GCT is characterized genetically by highly recurrent somatic mutations at the G34 position of the H3F3A gene, encoding the histone variant H3.3, in stromal cells. This leads to deregulated gene expression and increased proliferation of mutation-bearing cells. However, when GCT complicates Paget disease of bone (GCT/PDB) it behaves differently, showing a more malignant phenotype with 5-year survival less than 50%. GCT/PDB is caused by a germline mutation in the ZNF687 gene, which encodes a transcription factor involved in the repression of genes surrounding DNA double-strand breaks to promote repair by homologous recombination. Identification of these driver mutations led to novel diagnostic tools for distinguishing between these two tumors and other osteoclast-rich neoplasms. Herein, we review the clinical, histological, and molecular features of GCT in different contexts focusing also on pharmacological treatments.
摘要：
巨细胞瘤（GCT）是一种骨破坏性良性肿瘤，其特征是独特的多核破骨细胞样巨细胞具有溶骨特性，分布在肿瘤基质细胞中。GCT具有局部侵袭性，进行性侵袭邻近组织，偶尔表现出包括肺转移在内的恶性特征。GCT的遗传特征是在H3F3A基因的G34位置高度复发的体细胞突变，在基质细胞中编码组蛋白变体H3.3。这导致基因表达失调和携带突变的细胞的增殖增加。然而,当GCT使Paget骨病（GCT/PDB）复杂化时，其表现不同，表现出更恶性的表型，5年生存率低于50％。GCT/PDB是由ZNF687基因的种系突变引起的，它编码一种转录因子，该转录因子参与抑制DNA双链断裂周围的基因，以通过同源重组促进修复。这些驱动突变的鉴定导致了用于区分这两种肿瘤和其他富含破骨细胞的肿瘤的新型诊断工具。在这里，我们回顾了临床，组织学,和不同背景下GCT的分子特征也集中在药物治疗上。
