Chimeric Fusion Gene Analysis of Extraskeletal Myxoid Chondrosarcoma and its Pathologic Differential Diagnosis

骨外粘液样软骨肉瘤嵌合融合基因分析及病理鉴别诊断

• 批准号: 15590323
• 负责人: NOJIMA Takayuki
• 金额: $ 2.18万
• 依托单位: KANAZAWA MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590323/
• 关键词: extraskeletal myxoid chondrosarcoma; malignant soft tissue tumor; chimeric fusion gene; EWS gene; CHN gene; pathologic diagnosis

Extraskeletal myxoid chondrosarcoma (EMC) is known as a rare malignant soft tissue tumor. Recently, chromosomal rearrangements by the translocation, t(9;22), t(9;17), t(9;15), and t(3;9) have been identified in the many cases of EMC. These rearrangements result in gene fusions ; EWS-CHN, TAF2N-CHN, TCF12-CHN, and TFG-CHN. However, the function of fusion proteins is unknown. To examine the function of EWS-CHN fusion protein, we constructed an expression vector of EWS-CHN (pEC1.5). Several proteins in COS cells transfected with pEC1.5 were observed. To investigate the effect of fusion protein on the transcription, we performed luciferase reporter assay using the vector containing p21 promoter. The luciferase activity in COS cells transfected with pEC1.5 was lower than that of control. These results suggest that EWS-CHN fusion protein influences the expression level of some proteins, may be associated with p53 pathway and may exert oncogenic potential in EMC.We studied 22 cases of EMC by RT-PCR methods. EWS-CHN was detected in 10, TAF2N-CHN in 4 and TFG-CHN in one case. We identified novel EWS-CHN fusion junctions. We examined EWS or CHN gene rearrangement by FISH methods in five cases which were not able to detect a fusion gene by RT-PCR methods. We detected one EWS rearrangement and one CHN. However, there were no chimeric gene fusions in 15 cases of osteosarcoma, conventional chondrosarcoma and adenocarcinoma using by RT-PCR or FISH methods. These results suggest that these chimeric genes or gene rearrangements may be specific to EMC, and seem to be useful for pathologic diagnosis of EMC.

骨外黏液样软骨肉瘤是一种罕见的软组织恶性肿瘤。最近，在许多EMC病例中发现了易位t（9;22）、t（9;17）、t（9;15）和t（3;9）引起的染色体重排。这些重排导致基因融合；EWS-CHN, TAF2N-CHN, TCF12-CHN, TFG-CHN。然而，融合蛋白的功能尚不清楚。为了检验EWS-CHN融合蛋白的功能，我们构建了EWS-CHN表达载体pEC1.5。pEC1.5转染后，在COS细胞中观察到几种蛋白。为了研究融合蛋白对转录的影响，我们使用含有p21启动子的载体进行了荧光素酶报告基因实验。转染pEC1.5的COS细胞荧光素酶活性低于对照。这些结果提示EWS-CHN融合蛋白影响一些蛋白的表达水平，可能与p53通路有关，并可能在EMC中发挥致癌潜能。我们用RT-PCR方法对22例EMC进行了研究。EWS-CHN 10例，TAF2N-CHN 4例，TFG-CHN 1例。我们发现了新的EWS-CHN融合连接。我们用FISH方法检测了5例无法用RT-PCR方法检测到融合基因的EWS或CHN基因重排。我们检测到一个EWS重排和一个CHN。然而，RT-PCR或FISH方法在15例骨肉瘤、常规软骨肉瘤和腺癌中均未发现嵌合基因融合。这些结果表明，这些嵌合基因或基因重排可能是特异性的EMC，似乎有助于EMC的病理诊断。

项目成果

Ewing肉腫/PNETについて

关于尤文肉瘤/PNET

• 发表时间: 2004
• 期刊: 病理と臨床 22・3
• 作者: 石井壽晴;石川由起雄ほか;野島 孝之
• 通讯作者: 野島 孝之

The melanocyte inducing factor MITF is stably expressed in cell lines from human clear cell sarcoma.

• DOI: 10.1038/sj.bjc.6601212
• 发表时间: 2003-09-15
• 期刊: BRITISH JOURNAL OF CANCER
• 影响因子: 8.8
• 作者: Li, K K C;Goodall, J;Goding, C R;Liao, S-K;Wang, C-H;Lin, Y-C;Hiraga, H;Nojima, T;Nagashima, K;Schaefer, K-L;Lee, K A W
• 通讯作者: Lee, K A W

骨外性粘液型軟骨肉腫の電顕的観察

骨外粘液样软骨肉瘤的电镜观察

• 发表时间: 2003
• 期刊: 医生電顕技術誌 17
• 作者: Oikawa;K;Kuroda;M;et al.;Baba Y et al.;大兼政 良育
• 通讯作者: 大兼政 良育

Ultrastructural observation of extraskeletal myxoid chondrosarcoma.

骨外粘液样软骨肉瘤的超微结构观察。

• 发表时间: 2003
• 期刊: J.Electr.Microsc.Technol.Med.Biol. 17
• 作者: Y.Ohkanemasa;et al.
• 通讯作者: et al.

S.Lim, et al.: "Inactivation of RASSF1A in osteosarcoma"Oncology Reports. 10. 897-901 (2003)

S.Lim 等人：“骨肉瘤中 RASSF1A 的失活”肿瘤学报告。