Brody R I, Ueda T, Hamelin A, Jhanwar S C, Bridge J A, Healey J H, Huvos A G, Gerald W L, Ladanyi M
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Am J Pathol. 1997 Mar;150(3):1049-58.
The pathogenesis of myxoid chondrosarcoma (CS) is poorly understood. A recurrent translocation, t(9;22) (q22;q12), has been recognized in CS, specifically in extraskeletal myxoid CS. Recently, this translocation has been shown to represent a rearrangement of the EWS gene at 22q12 with a novel gene at 9q22 designated CHN (or TEC). Sequence analysis suggests that CHN encodes a novel orphan nuclear receptor with a zinc finger DNA-binding domain. The structure of this gene fusion has been characterized in only a limited number of extraskeletal myxoid CSs and its presence in other types of CS has not been extensively examined. We studied 46 cases of CS (8 extraskeletal myxoid, 4 skeletal myxoid, 4 mesenchymal, and 30 other) for the EWS/CHN gene fusion by reverse transcriptase polymerase chain reaction, Southern blotting, and long-range DNA polymerase chain reaction. The EWS/CHN gene fusion was present in 6 of 8 extraskeletal myxoid CSs and was not detected in any of the remaining cases, including the 4 skeletal myxoid CSs. The negative findings in the latter cases suggest that skeletal myxoid CS is pathogenetically distinct from its extraskeletal counterpart. Notably, 2 cases of extraskeletal myxoid CS showed neither an EWS/CHN fusion transcript nor EWS/CHN genomic fusion nor EWS or CHN genomic rearrangement, suggesting genetic heterogeneity within extraskeletal myxoid CS. Finally, we also provide evidence for alternative splicing of the 3' end of the fusion transcript. Extraskeletal myxoid CS thus represents yet another sarcoma type containing a gene fusion involving EWS.
黏液样软骨肉瘤（CS）的发病机制尚不清楚。一种复发性易位，t(9;22) (q22;q12)，已在CS中被识别，特别是在骨外黏液样CS中。最近，这种易位已被证明代表22q12处EWS基因与9q22处一个名为CHN（或TEC）的新基因的重排。序列分析表明，CHN编码一种具有锌指DNA结合结构域的新型孤儿核受体。这种基因融合的结构仅在少数骨外黏液样CS中得到表征，其在其他类型CS中的存在尚未得到广泛研究。我们通过逆转录聚合酶链反应、Southern印迹和长程DNA聚合酶链反应，研究了46例CS（8例骨外黏液样、4例骨内黏液样、4例间充质和30例其他类型）中的EWS/CHN基因融合情况。EWS/CHN基因融合存在于8例骨外黏液样CS中的6例，而在其余病例中均未检测到，包括4例骨内黏液样CS。后一类病例的阴性结果表明，骨内黏液样CS在发病机制上与其骨外对应物不同。值得注意的是，2例骨外黏液样CS既未显示EWS/CHN融合转录本，也未显示EWS/CHN基因组融合，也未显示EWS或CHN基因组重排，提示骨外黏液样CS内存在遗传异质性。最后，我们还提供了融合转录本3'端选择性剪接的证据。因此，骨外黏液样CS代表了另一种含有涉及EWS基因融合的肉瘤类型。
