Molecular diagnosis of pediatric solid tumor

据报道，许多人类肿瘤都含有特征性的染色体易位。通过染色体易位，产生特定的融合基因。这些融合基因被认为在肿瘤发生中发挥重要作用。尤文肉瘤和PNET具有相同的染色体易位，t(11；22)，并通过该易位产生EWS-FLI-1融合基因。Fli-1是融合基因的伴侣，是ETS家族转录因子的成员。ETS家族的其他成员ERG和ETV1也分别通过t(21；22)和t(7；22)与EWS融合。最近，我们在一例尤文氏肉瘤中发现了一个新的融合基因EWS-Elaf。由于融合基因分析显示尤文氏肉瘤和PNET具有相同的融合转录本，尤文氏肉瘤和PNDT被认为属于共同的实体。在这份报告中，我们对一个新的融合基因EWS-Elaf进行了广泛而详细的鉴定，包括全长cDNA序列、RNA印迹分析、DNA印迹分析和染色体分析。EWS-Elaf基因是诊断尤文肉瘤的又一融合基因，参与尤文肉瘤的发生发展。此外，我们还进行了尤文肿瘤家族的基因分析，并与免疫组织化学和超微结构分析相关联。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；从不到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致癌机制提供了进一步的重要信息。

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.