c-kit gene mutation is common and widely distributed in intracranial germinomas

c-kit基因突变在颅内生殖细胞瘤中常见且广泛分布

基本信息

  • 批准号:
    15591514
  • 负责人:
  • 金额:
    $ 1.66万
  • 依托单位:
  • 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

项目摘要

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 … More 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. Less
目标:随着积极的多模式治疗的出现,颅内生殖细胞肿瘤(IGCT)正在得到良好的控制;然而,10%的生殖细胞瘤和许多非生殖细胞瘤亚型仍然难以治疗。本研究的目的是研究酪氨酸激酶受体(KIT)在IGCT中的表达和遗传学改变,针对IGCT,已开始或计划在几种肿瘤中使用甲磺酸伊马替尼进行分子靶向治疗。方法:采用正交试验设计26个连续IGCT,包括13个生殖细胞瘤,5个混合生殖细胞瘤(MGCT),4个未成熟畸胎瘤(IT)和两个卵黄囊瘤(YST)和绒毛膜癌,进行了检查。在石蜡切片上进行KIT和CD 34的免疫组化,并通过PCR-SSCP在有或没有预筛选的情况下在外显子2、8-11、13和17中完成c-kit突变分析。在IGCT和其他脑肿瘤的组织学亚型中,KIT在细胞膜上强烈表达 ...更多信息 在生殖细胞瘤细胞、生殖细胞瘤(100%)和MGCT(80%)中,以及在IT的分化上皮细胞和平滑肌细胞的细胞质中。CD 34在MGCTs(60%)、ITs(100%)和绒毛膜癌(50%)的肿瘤细胞和非生殖细胞瘤成分的软骨细胞中呈膜表达,而在生殖细胞瘤细胞中不表达。在3例生殖细胞瘤中共检测到5个c-kit错义突变,分别位于外显子2、11、13和17。首次在单个肿瘤中检测到E73 K、T96 M(均为外显子2)和A636 V(外显子13)三种突变。c-kit基因突变与患者预后无关。结论:KIT免疫组化有助于生殖细胞瘤的正确诊断。考虑到这里采用的是低灵敏度的方法,推测生殖细胞瘤中c-kit突变的真实的频率和分布分别更高和更广。本研究有望为阐明生殖细胞瘤的发病机制和甲磺酸伊马替尼的临床应用奠定基础。少

项目成果

期刊论文数量(34)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Cyanotic breath-holding spell : a life-threatening complication after radical resection of a cervicomedullary ganglioglioma. Case report
紫绀型屏气发作:颈髓神经节胶质瘤根治性切除术后危及生命的并发症。
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Fujisawa H;Yoshida Y;Niida Y;Hasegawa M;Yamashita J
  • 通讯作者:
    Yamashita J
Hayashi Ya, Fujikawa H, et al.: "Penetrating head injury caused by bear claws : case report"J Trauma. 55. 1178-1180 (2003)
Hayashi Ya、Fujikawa H 等人:“熊爪造成的头部穿透伤:病例报告”J 创伤。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Molecular analysis of the rhabdoid predisposition syndrome in a child:: a novel germline hSNF5/INI1 mutation and absence of c-myc amplification
  • DOI:
    10.1023/a:1024345221792
  • 发表时间:
    2003-07-01
  • 期刊:
  • 影响因子:
    3.9
  • 作者:
    Fujisawa, H;Takabatake, Y;Yamashita, J
  • 通讯作者:
    Yamashita, J
Recurrent intracranial solitary fibrous tumor with cerebrospinal fluid dissemination. Case report.
  • DOI:
    10.3171/jns.2004.101.6.1045
  • 发表时间:
    2004-12
  • 期刊:
  • 影响因子:
    4.1
  • 作者:
    K. Miyashita;Y. Hayashi;H. Fujisawa;M. Hasegawa;J. Yamashita
  • 通讯作者:
    K. Miyashita;Y. Hayashi;H. Fujisawa;M. Hasegawa;J. Yamashita
CT arteriography for orbital tumors: Diagnostic and surgical value
  • DOI:
    10.1016/j.jocn.2004.08.012
  • 发表时间:
    2005-06-01
  • 期刊:
  • 影响因子:
    2
  • 作者:
    Hasegawa, M;Fujisawa, H;Matsui, O
  • 通讯作者:
    Matsui, O
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FUJISAWA Hironori其他文献

FUJISAWA Hironori的其他文献

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{{ truncateString('FUJISAWA Hironori', 18)}}的其他基金

Spontaneous polarization in nanosized ferroelectrics and its size dependence
纳米铁电体的自发极化及其尺寸依赖性
  • 批准号:
    24656214
  • 财政年份:
    2012
  • 资助金额:
    $ 1.66万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Efficient multiple testing methods for genome data
高效的基因组数据多重检测方法
  • 批准号:
    22500269
  • 财政年份:
    2010
  • 资助金额:
    $ 1.66万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Preparation of composition-and valence-controlled BiFeO_3 thin films and investigation of leakage mechanism
成分和价态控制的BiFeO_3薄膜的制备及泄漏机理研究
  • 批准号:
    22656075
  • 财政年份:
    2010
  • 资助金额:
    $ 1.66万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Study on fabrication and polarization switching of nanosized ferroelectrics
纳米铁电体的制备及极化切换研究
  • 批准号:
    20760202
  • 财政年份:
    2008
  • 资助金额:
    $ 1.66万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Robust inference and its application to genome data
稳健推理及其在基因组数据中的应用
  • 批准号:
    19700270
  • 财政年份:
    2007
  • 资助金额:
    $ 1.66万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
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