Molecular diagnosis of pediatric solid tumor

现在许多人类肿瘤被报道含有特征性的染色体易位。通过染色体易位，产生特异性融合基因。这些融合基因被认为在肿瘤发生中起重要作用。尤文肉瘤和PNET具有相同的特异性染色体易位t（11 ; 22），通过该易位产生EWS-FLI-1融合基因。FLI-1是Ets家族转录因子中的一员，是融合基因的伴侣。Ets家族基因的其他成员ERG和ETV 1也分别通过t（21 ; 22）和t（7 ; 22）与EWS融合。最近，我们发现了一个新的融合基因，EWS-ElAF在尤文氏肉瘤的情况下。由于融合基因的分析显示，尤文肉瘤和PNET具有相同的融合转录本，尤文肉瘤和PNDT被认为属于一个共同的实体。本文对一个新的融合基因EWS-ElAF进行了详细的cDNA序列测定、RNA印迹分析、DNA印迹分析和染色体分析。EWS-ElAF基因是尤文肉瘤诊断中的又一个融合基因，并参与尤文肉瘤的发生。并结合免疫组化和超微结构分析对尤文家族肿瘤进行了遗传学分析。从这些分析中，揭示了几个发现：遗传分析和组织病理学分析的局限性;神经源性表型和嵌合体基因之间的关系，从小于1 mm^3的活检样本中诊断尤文家族肿瘤。本研究结果为尤文家族肿瘤的诊断和发生提供了进一步的有意义的信息。

Many human tumors are now reported to contain characteristic chromosomal translocations. Through the chromosomal translocations, the specific fusion genes are generated. These fusion genes are considered to play an important role in oncogenesis. Ewing' sarcoma and PNET have the same specific chromosomal translocation, t(11 ; 22) and through this translocation, EWS-FLI-1 fusion gene was generated. FLI-1, a partner of the fusion gene, is a member of the Ets family transcription factors. Other members of the Ets family genes, ERG and ETV1, are also fused to EWS through t(21 ; 22) and t(7 ; 22), respectively. Recently, we identified a new fusion gene, EWS-ElAF in a case of Ewing's sarcoma. Since analysis of the fusion genes revealed that Ewing's sarcoma and PNET has the same fusion transcripts, Ewing's sarcoma and PNDT are considered to belong to a common entity. In this report, we extensively characterized a new fusion gene, EWS-ElAF, in detail ; whole cDNA sequence, RNA blot analysis, DNA blot analysis and chromosomal analysis. EWS-ElAF gene is conclusively found to be another fusion gene available for the diagnosis of Ewing's sarcoma and participate in the oncogenesis of Ewing's sarcoma. Furthermore, we have done the genetic analysis of Ewing family of tumors in correlation with immunohistochemical analysis and ultrastructural analysis. From these analyses, several findings were revealed ; limitations of both genetic analysis and histopathological analysis ; relationship between neurogenic phenotypes and chimera genes, diagnosis of Ewing family of tumors from less than 1 mm^3 of biopsy samples. The present findings provide us further significant information concerning the diagnosis and the oncogenesis of Ewing family of tumors.