MYC and EIF3H Coamplification significantly improve response and survival of non-small cell lung cancer patients (NSCLC) treated with gefitinib.
MYC and EIF3H Coamplification significantly improve response and survival of non-small cell lung cancer patients (NSCLC) treated with gefitinib.
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DOI：
10.1097/jto.0b013e31819a5767
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发表时间：
2009-04
期刊：
影响因子：
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通讯作者：
Gemmill R
中科院分区：
文献类型：
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作者：
Cappuzzo F;Varella-Garcia M;Rossi E;Gajapathy S;Valente M;Drabkin H;Gemmill R
我们研究了非小细胞肺癌(NSCLC)患者中真核细胞翻译起始因子3亚单位H(EIF3)和MYC基因扩增的发生率，以及MYC/EIF3 H基因拷贝数增加是否影响对表皮生长因子受体酪氨酸激酶抑制剂的反应。采用自行设计的三色DNA探针，采用荧光原位杂交(FISH)技术，对54例接受吉非替尼治疗的转移性非小细胞肺癌患者的EIF3 H和MYC基因进行了分析。EIFH扩增10例(18.5%)，MYC共扩增10例(18.5%)。2例(3.7%)有MYC扩增，但无EIFH共扩增。通过接收器工作特性分析确定MYC和EIF3H拷贝数的分界值，以最好地区分敏感和耐药群体。MYC FISH阳性患者(MYC+，平均≥2.8)的有效率(P=0.003.0 5)、进展时间(P=0.0 1)和总生存期(OS：P=0.0 2)显著高于MYC−(平均为2.8)。同样，EIF3HFISH阳性患者(EIF3H+，平均≥2.75)的有效率(P=0.002)、进展时间(P=0.01)和OS(P=0.01)显著高于EIF3H−(平均为2.75)。我们的结果表明，MYC和EIF3H在非小细胞肺癌中经常是共扩增的，并且高拷贝数与表皮生长因子受体酪氨酸激酶抑制剂敏感性的增加有关。
We investigated the incidence of eukaryotic translation initiation factor 3 subunit H (EIF3H) and MYC amplification in non-small cell lung cancer (NSCLC) patients, and whether MYC/EIF3H increased gene copy number affected response to Epidermal Growth Factor Receptor tyrosine kinase inhibitors. Metastatic NSCLC patients (n = 54) treated with gefitinib were analyzed for the genomic content of EIF3H and MYC genes by fluorescence in situ hybridization (FISH) using a custom-designed 3-color DNA probe set. Amplification of EIF3H (ratio EIF3H/CEP8 >2), was observed in 10 cases (18.5%), and MYC was coamplified in all. MYC amplification without coamplification of EIF3H was observed in 2 cases (3.7%). Receiver operating characteristic analysis was conducted to identify the cutoff for MYC and EIF3H copy number best discriminating sensitive and resistant populations. MYC FISH positive patients (MYC+, mean ≥2.8) had a significantly higher response rate (p = 0.003), longer time to progression (p = 0.01) and overall survival (OS: p = 0.02) than MYC− (mean <2.8). Similarly, EIF3H FISH positive patients (EIF3H+, mean ≥2.75) had a significantly higher response rate (p = 0.002), longer time to progression (p = 0.01) and OS (p = 0.01) than EIF3H− (mean <2.75). Our results indicate that MYC and EIF3H are frequently coamplified in NSCLC and that a high copy number correlates with increased epidermal growth factor receptor tyrosine kinase inhibitors sensitivity.