Fibroblast growth factor receptor 4 mutation and polymorphism in Japanese lung cancer

Fibroblast growth factor receptor 4 mutation and polymorphism in Japanese lung cancer
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DOI:
10.3892/or_00000119
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发表时间:
2008-11-01
期刊:
影响因子:
4.2
通讯作者:
Fujii, Yoshitaka
Fujii, Yoshitaka
中科院分区:
医学3区
文献类型:
--
作者:
Sasaki, Hidefumi;Okuda, Katsuhiro;Fujii, Yoshitaka

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我们研究了手术治疗的非小细胞肺癌(NSCLC)患者的FGFR4激活区突变状态和388位密码子的单核苷酸多态性(SNP)。用直接测序法分析有无FGFR4突变(n=147),用LightCycler杂交探针分型分析FGFR4 Arg388等位基因的存在(n=387)。我们的肺癌患者中不存在FGFR4突变。在61.8%的患者中,存在纯合子或杂合子Arg388等位基因。FGFR4基因与性别、吸烟状况、病理亚型等临床病理特征无相关性。EGFR突变状态与FGFR4基因在肺癌中的分布无关。在淋巴结阴性的患者中,FGFR4基因与疾病预后无关,而在淋巴结阳性的患者中,FGFR4 Arg388与较差的生存率显著相关。这种关联并不归因于患者对辅助化疗的反应。因此,FGFR4基因多态是日本晚期非小细胞肺癌患者的预后指标。
We investigated the FGFR4 mutation status at the kinase domain and FGFR4 single nucleotide polymorphism (SNP) at codon 388 in surgically treated non-small cell lung cancer (NSCLC) cases. The presence or absence of FGFR4 mutations of kinase domains was analyzed by direct sequences (n=147), and the presence of FGFR4 Arg388 allele was analyzed by genotyping assay using LightCycler hybridization probes (n=387). FGFR4 mutations were not present in our lung cancer patients. In 61.8% of patients, homo- or heterozygous Arg388 allele was present. No correlation existed between the FGFR4 genotype and clinicopathological features such as gender, smoking status and pathological subtypes. EGFR mutation status was not correlated with the FGFR4 genotype of lung cancers. In node-negative patients, the FGFR4 genotype was not correlated with disease outcome, while in the node-positive patients FGFR4 Arg388 was significantly associated with worse survival. This association was not attributed to patient response to adjuvant chemotherapy. Therefore, the role of FGFR4 polymorphism is a prognostic marker for advanced NSCLC in Japanese patients.