Department of Pathology, Leiden University Medical Center, Leiden, Netherlands.
BMC Cancer. 2009 Nov 10;9:393. doi: 10.1186/1471-2407-9-393.
Chondroblastoma is a benign cartilaginous tumour of bone that predominantly affects the epiphysis of long bones in young males. No recurrent chromosomal re-arrangements have so far been observed.
We identified an index case with a balanced translocation by Combined Binary Ratio-Fluorescent in situ Hybridisation (COBRA-FISH) karyotyping followed by breakpoint FISH mapping and array-Comparative Genomic Hybridisation (aCGH). Candidate region re-arrangement and candidate gene expression were subsequently investigated by interphase FISH and immunohistochemistry in another 14 cases.
A balanced t(5;17)(p15;q22-23) was identified. In the index case, interphase FISH showed that the translocation was present only in mononucleated cells and was absent in the characteristic multinucleated giant cells. The t(5;17) translocation was not observed in the other cases studied. The breakpoint in 5p15 occurred close to the steroid reductase 5alpha1 (SRD5A1) gene. Expression of the protein was found in all cases tested. Similar expression was found for the sex steroid signalling-related molecules oestrogen receptor alpha and aromatase, while androgen receptors were only found in isolated cells in a few cases. The breakpoint in 17q22-23 was upstream of the carbonic anhydrase x (CA10) gene region and possibly involved gene-regulatory elements, which was indicated by the lack of CA10 protein expression in the index case. All other cases showed variable levels of CA10 expression, with low expression in three cases.
We report a novel t(5;17)(p15;q22-23) translocation in chondroblastoma without involvement of any of the two chromosomal regions in other cases studied. Our results indicate that the characteristic multinucleated giant cells in chondroblastoma do not have the same clonal origin as the mononuclear population, as they do not harbour the same translocation. We therefore hypothesise that they might be either reactive or originate from a distinct neoplastic clone, although the occurrence of two distinct clones is unlikely. Impairment of the CA10 gene might be pathogenetically relevant, as low expression was found in four cases. Diffuse expression of SRD5A1 and sex steroid signalling-related molecules confirms their role in neoplastic chondrogenesis.
成软骨细胞瘤是一种良性软骨源性肿瘤，主要影响年轻男性长骨的骨骺。目前尚未观察到复发性染色体重排。
我们通过组合二元比荧光原位杂交（COBRA-FISH）核型分析，随后进行断点荧光原位杂交定位和阵列比较基因组杂交（aCGH），鉴定了一个平衡易位的索引病例。随后，通过间期荧光原位杂交和免疫组织化学在另外 14 例中研究候选区域重排和候选基因表达。
鉴定出一个平衡易位 t(5;17)(p15;q22-23)。在索引病例中，间期荧光原位杂交显示易位仅存在于单核细胞中，而不存在于特征性多核巨细胞中。在研究的其他病例中未观察到 t(5;17)易位。5p15 处的断点靠近类固醇还原酶 5alpha1（SRD5A1）基因。所有检测的病例均发现该蛋白的表达。在所有测试的病例中，发现了与性类固醇信号相关的分子雌激素受体 alpha 和芳香酶的相似表达，而雄激素受体仅在少数病例的孤立细胞中发现。17q22-23 处的断点位于碳酸酐酶 x（CA10）基因区域的上游，可能涉及基因调节元件，这表明索引病例中缺乏 CA10 蛋白表达。所有其他病例均显示 CA10 表达水平不同，其中 3 例表达水平较低。
我们报告了软骨母细胞瘤中的一种新的 t(5;17)(p15;q22-23)易位，而在其他研究病例中未涉及这两个染色体区域中的任何一个。我们的结果表明，软骨母细胞瘤中的特征性多核巨细胞与单核细胞群并非具有相同的克隆起源，因为它们不具有相同的易位。因此，我们假设它们可能是反应性的，或者来自于一个不同的肿瘤克隆，尽管不太可能出现两个不同的克隆。CA10 基因的失活可能与发病机制有关，因为在 4 例中发现表达水平较低。SRD5A1 和性类固醇信号相关分子的弥漫表达证实了它们在肿瘤性软骨发生中的作用。
