KIKUCHI Haruhiro Keio University, School of Medicine, Instructor, 医学部・中央検査室, 助手 (10161423)
HATA Jun-ichi Keio University, School of Medicine, Professor, 医学部・病理学教室, 教授 (90051614)
|Budget Amount *help
¥3,100,000 (Direct Cost : ¥3,100,000)
Fiscal Year 1998 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1997 : ¥2,000,000 (Direct Cost : ¥2,000,000)
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.