Lee Jen-Chieh, Liang Cher-Wei, Fletcher Christopher Dm
Department and Graduate Institute of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Mod Pathol. 2017 May;30(5):728-733. doi: 10.1038/modpathol.2016.236. Epub 2017 Jan 13.
Giant cell tumors of bone are locally aggressive bone neoplasms with a predilection for young adults. Histologically, they are composed of histiocytoid to spindled mononuclear cells, admixed with numerous large osteoclastic giant cells. Giant cell tumors of soft tissue are rare tumors that bear striking histological resemblance to giant cell tumors of bone and might be regarded as a soft tissue analog thereof. Point mutations of the H3F3A gene (coding for a histone H3.3 protein) at the Gly34 codon, mostly G34W resulting from a GGG>TGG nucleotide change, have recently been identified in a vast majority of giant cell tumors of bone. To delineate the possible pathogenic linkage between both tumor types, we analyzed the H3F3A genotypes in a series of 15 giant cell tumors of soft tissue by Sanger sequencing and found no mutation in any case. We then sequenced cognate histone H3 genes with an identical nucleotide sequence ('GGG') at the codon Gly34, including the H3F3B, H3F3C, HIST2H3A, HIST2H3C, and HIST2H3D genes, and no somatic mutation was detected. These results reveal that giant cell tumors of soft tissue are probably genetically distinct from their bone counterparts and suggest that they might be pathogenically unrelated. Given the prominence of non-neoplastic cells in these tumors and the limitations of the current study, however, analyses using more sensitive techniques might be required to solve the issue.
骨巨细胞瘤是具有局部侵袭性的骨肿瘤，好发于年轻人。在组织学上，它们由组织细胞样至梭形单核细胞组成，并混有大量大的破骨细胞样巨细胞。软组织巨细胞瘤是罕见肿瘤，在组织学上与骨巨细胞瘤有显著相似之处，可被视为骨巨细胞瘤的软组织类似物。最近在绝大多数骨巨细胞瘤中发现了H3F3A基因（编码组蛋白H3.3蛋白）第34密码子甘氨酸处的点突变，大多是由GGG>TGG核苷酸变化导致的G34W突变。为了阐明这两种肿瘤类型之间可能的致病联系，我们通过桑格测序分析了15例软组织巨细胞瘤系列中的H3F3A基因型，结果在任何病例中均未发现突变。然后我们对密码子34处具有相同核苷酸序列（“GGG”）的同源组蛋白H3基因进行测序，包括H3F3B、H3F3C、HIST2H3A、HIST2H3C和HIST2H3D基因，未检测到体细胞突变。这些结果表明，软组织巨细胞瘤在遗传上可能与其骨对应物不同，并提示它们在致病方面可能无关。然而，鉴于这些肿瘤中非肿瘤细胞的突出性以及本研究的局限性，可能需要使用更敏感的技术进行分析来解决这一问题。
