神经母细胞瘤中不存在GIST型c-kit功能获得性突变。
No GIST-type c-kit gain of function mutations in neuroblastic tumours.
作者信息
Korja M, Finne J, Salmi T T, Haapasalo H, Tanner M, Isola J
机构信息
Department of Medical Biochemistry and Molecular Biology, University of Turku, Kiinamyllynkatu 10, FI-20520 Turku, Finland.
出版信息
J Clin Pathol. 2005 Jul;58(7):762-5. doi: 10.1136/jcp.2004.024331.
AIMS
Neuroblastic tumours (NTs) have been shown to respond to imatinib treatment in vivo and in vitro, possibly via inactivating the c-kit receptor. The purpose of this study was to identify gastrointestinal stromal tumour (GIST)-type c-kit gene associated mutations in exons 9, 11, 13, and 17 in NTs to recognise a subset of tumours that would probably respond to imatinib treatment.
METHODS
Expression of the c-kit protein was detected immunohistochemically in a total of 37 archival paraffin wax embedded NTs using polyclonal rabbit antihuman c-kit antibody. After immunohistochemistry, c-kit gene associated chromosomal mutations in all cases of NT were detected with denaturing high performance liquid chromatography (HPLC).
RESULTS
Denaturing HLPC analysis did not reveal GIST-type mutations in four immunohistochemically detected c-kit positive or in 33 c-kit negative NTs.
CONCLUSIONS
c-kit receptor expression and GIST-type c-kit gene mutations are rare events in NTs. Oncogenic activation of c-kit in NTs presumably differs from that of GISTs, which may influence their responsiveness to imatinib treatment. Whether c-kit has an essential role in the pathogenesis of NTs remains to be investigated.
目的
已证实神经母细胞瘤（NTs）在体内和体外对伊马替尼治疗有反应，可能是通过使c-kit受体失活。本研究的目的是在NTs的第9、11、13和17外显子中鉴定胃肠道间质瘤（GIST）型c-kit基因相关突变，以识别可能对伊马替尼治疗有反应的肿瘤亚群。
方法
使用多克隆兔抗人c-kit抗体，通过免疫组织化学方法在总共37例存档石蜡包埋的NTs中检测c-kit蛋白的表达。免疫组织化学后，采用变性高效液相色谱（HPLC）检测所有NTs病例中与c-kit基因相关的染色体突变。
结果
变性HLPC分析未在4例免疫组织化学检测为c-kit阳性的NTs或33例c-kit阴性的NTs中发现GIST型突变。
结论
c-kit受体表达和GIST型c-kit基因突变在NTs中是罕见事件。NTs中c-kit的致癌激活可能与GIST不同，这可能影响它们对伊马替尼治疗的反应性。c-kit在NTs发病机制中是否起关键作用仍有待研究。
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