@techreport{oai:kanazawa-u.repo.nii.ac.jp:00056885,
 month = {Jul},
 note = {期間中に以下の4つのテーマについて研究した.
(1)Atypical teratoid/rhabdoid tumorにおけるEMA, SMAの発現とhSNF5/INI1遺伝子の変異解析
(2)髄芽腫における免疫組織学的および細胞遺伝学的異常とその臨床的意義 〜c-,N-mycおよびβ-,γ-カテニン,cyclin D1に着目して〜
(3)Atypical teratoid/rhabdoid tumorにおけるcyclin D1の発現とその意義
(4)頭蓋内胚細胞性腫瘍におけるKITの発現とc-kit遺伝子の変異解析
(1)の成果は,症例報告として2003年国際医学雑誌Journal of Neuro-oncologyに発表した.
(2)の成果は、2005年米国脳神経外科学会誌Journal of Neurosurgery (Pediatrics)に発表した.
(3)の研究は,AT/RTが誤診されている可能性を検討するため,(1)で得られた知見を応用し3歳以下の悪性脳腫瘍の自験16例を解析したものである.結果の要約は,1)5例(31%)がAT/RTと診断された.2)cyclin D1の過剰発現はhSNF5/INI1遺伝子の不活化と相関した.以上より、AT/RTの高い誤診率の低減にcyclin D1の免疫染色が有用であることが示唆された.本成果は、2005年国際医学雑誌Journal of Neuro-oncologyに受理され,印刷中である.
(4)の研究は、当院で経験した頭蓋内胚細胞性腫瘍26例について、近年分子標的薬イマチニブに高い感受性を示すことが知られるチロシンキナーゼ受容体KITの発現と責任遺伝子c-kitの変異,CD34の発現を解析した.その結果,KITはgerminomaおよびmixed germ cell tumorのgerminomatous成分の腫瘍細胞膜のみに高発現が認められた.c-kitの変異は3例のgerminoma(13例中3例,23%)において,計5個検出された.いずれもミスセンス変異であり,機能獲得性作用が示唆された.これら変異に対するイマチニブの効果は明らかでなく,今後検討が必要である.本研究は,頭蓋内胚細胞性腫瘍においてKITの発現と同時にc-kit変異を解析した初めての報告であり,現在、国際医学雑誌に投稿中である., OBJECT : With the advent of aggressive multimodality therapy, intracranial germ cell tumors (IGCTs) are becoming favorably controlled ; however, 10% of the germinomas and many of the nongerminomatous subtypes remain refractory to therapy. The goal of this study was to investigate the expression and genetic alteration of the tyrosine kinase receptor, KIT, in IGCTs for which molecular targeting therapy with imatinib mesylate has been commenced or planned in several kinds of neoplasms. METHODS : Twenty-six consecutive IGCTs, including thirteen germinomas, five mixed germ cell tumors (MGCTs), four immature teratomas (ITs) and two each of yolk sac tumors (YSTs) and choriocarcinomas, were examined. Immunohistochemistry for KIT and CD34 was performed on paraffin sections and c-kit mutation analysis was accomplished in exons 2, 8-11, 13 and 17 with or without prescreening by PCR-SSCP. Among the histologic subtypes of IGCTs and other brain tumors, KIT was strongly expressed at the cell membrane of germinoma cells, germinomas (100%) and MGCTs (80%), and in the cytoplasm of differentiated epithelial and smooth muscle cells of ITs. In contrast, the membranous expression of CD34 was detected in the tumor cells and the chondrocytes of the nongerminomatous component of MGCTs (60%), ITs (100%) and choriocarcinoma (50%), but not in germinoma cells. A total of five missense mutations of c-kit were detected in three germinomas (23%) and they were distributed in exons 2, 11, 13 and 17. Three mutations, E73K, T96M (both exon 2) and A636V (exon 13), were detected for the first time in a single tumor. The c-kit mutations were not correlated with patient's prognosis. CONCLUSIONS : KIT immunohistochemistry is useful for the correct diagnosis of germinoma. Considering that low sensitivity methods were employed here, the real frequency and distribution of the c-kit mutation in germinomas are speculated to be higher and broader, respectively. This study is expected to contribute to the clarification of the pathogenesis of germinoma and the future clinical use of imatinib mesylate., 研究課題/領域番号:15591514, 研究期間(年度):2003 – 2004, 出典：「小児悪性脳腫瘍における包括的遺伝子解析と分子診断法の確立」研究成果報告書　課題番号15591514
（KAKEN：科学研究費助成事業データベース（国立情報学研究所））
（https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-15591514/155915142004kenkyu_seika_hokoku_gaiyo/)を加工して作成, 金沢大学医学部附属病院},
 title = {小児悪性脳腫瘍における包括的遺伝子解析と分子診断法の確立},
 year = {2006}
}