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首页> 外文期刊>BMC Medical Genomics >Genome wide SNP comparative analysis between EGFR and KRAS mutated NSCLC and characterization of two models of oncogenic cooperation in non-small cell lung carcinoma
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Genome wide SNP comparative analysis between EGFR and KRAS mutated NSCLC and characterization of two models of oncogenic cooperation in non-small cell lung carcinoma

机译：EGFR和KRAS突变的NSCLC之间的全基因组SNP比较分析和两种非小细胞肺癌致癌合作模型的表征

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Background Lung cancer with EGFR mutation was shown to be a specific clinical entity. In order to better understand the biology behind this disease we used a genome wide characterization of loss of heterozygosity and amplification by Single Nucleotide Polymorphism (SNP) Array analysis to point out chromosome segments linked to EGFR mutations. To do so, we compared genetic profiles between EGFR mutated adenocarcinomas (ADC) and KRAS mutated ADC from 24 women with localized lung cancer. Results Patterns of alterations were different between EGFR and KRAS mutated tumors and specific chromosomes alterations were linked to the EGFR mutated group. Indeed chromosome regions 14q21.3 (p = 0.027), 7p21.3-p21.2 (p = 0.032), 7p21.3 (p = 0.042) and 7p21.2-7p15.3 (p = 0.043) were found significantly amplified in EGFR mutated tumors. Within those regions 3 genes are of special interest ITGB8 , HDAC9 and TWIST1 . Moreover, homozygous deletions at CDKN2A and LOH at RB1 were identified in EGFR mutated tumors. We therefore tested the existence of a link between EGFR mutation, CDKN2A homozygous deletion and cyclin amplification in a larger series of tumors. Indeed, in a series of non-small-cell lung carcinoma (n = 98) we showed that homozygous deletions at CDKN2A were linked to EGFR mutations and absence of smoking whereas cyclin amplifications ( CCNE1 and CCND1 ) were associated to TP53 mutations and smoking habit. Conclusion All together, our results show that genome wide patterns of alteration differ between EGFR and KRAS mutated lung ADC, describe two models of oncogenic cooperation involving either EGFR mutation and CDKN2A deletion or cyclin amplification and TP53 inactivating mutations and identified new chromosome regions at 7p and 14q associated to EGFR mutations in lung cancer.
机译：背景技术EGFR突变的肺癌被证明是特定的临床实体。为了更好地了解这种疾病的生物学特性，我们使用了单核苷酸多态性（SNP）阵列分析对杂合性丧失和扩增进行全基因组表征，以指出与EGFR突变相关的染色体片段。为此，我们比较了来自24例局灶性肺癌女性的EGFR突变腺癌（ADC）和KRAS突变ADC之间的遗传特征。结果EGFR和KRAS突变的肿瘤的改变方式不同，特定的染色体改变与EGFR突变的组有关。实际上，发现染色体区域14q21.3（p = 0.027），7p21.3-p21.2（p = 0.032），7p21.3（p = 0.042）和7p21.2-7p15.3（p = 0.043）被显着扩增在EGFR突变的肿瘤中。在那些区域内，有3个基因特别令人感兴趣ITGB8，HDAC9和TWIST1。此外，在EGFR突变的肿瘤中鉴定出CDKN2A和RB1处的LOH纯合缺失。因此，我们在更大系列的肿瘤中测试了EGFR突变，CDKN2A纯合缺失和细胞周期蛋白扩增之间的联系。实际上，在一系列非小细胞肺癌（n = 98）中，我们显示CDKN2A的纯合缺失与EGFR突变和无吸烟有关，而细胞周期蛋白扩增（CCNE1和CCND1）与TP53突变和吸烟习惯有关。结论总之，我们的结果表明，EGFR和KRAS突变的肺ADC之间的全基因组改变模式不同，描述了两种致癌合作模型，涉及EGFR突变和CDKN2A缺失或细胞周期蛋白扩增和TP53失活突变，并在7p和7p处鉴定了新的染色体区域。与肺癌中EGFR突变相关的14q。

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