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.
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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EGFR和KRAS突变的NSCLC之间的基因组广泛的SNP比较分析以及非小细胞肺癌中的两种致癌合作模型的表征。
DOI：
10.1186/1755-8794-1-25
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发表时间：
2008-06-12
影响因子：
2.7
通讯作者：
Laurent-Puig, Pierre
中科院分区：
文献类型：
--
作者：
Blons, Helene;Pallier, Karine;Le Corre, Delphine;Danel, Claire;Tremblay-Gravel, Maxime;Houdayer, Claude;Fabre-Guillevin, Elizabeth;Riquet, Marc;Dessen, Philippe;Laurent-Puig, Pierre
EGFR突变的肺癌是一种特殊的临床实体。为了更好地理解这种疾病背后的生物学，我们使用了全基因组的杂合性缺失表征和通过单核苷酸多态性（SNP）阵列分析的扩增，以指出与EGFR突变相关的染色体片段。为此，我们比较了24例局部肺癌患者EGFR突变型腺癌（ADC）和KRAS突变型ADC之间的基因谱。EGFR和KRAS突变肿瘤之间的改变模式不同，并且特定的染色体改变与EGFR突变组相关。事实上，在EGFR突变的肿瘤中发现染色体区域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）显著扩增。在这些区域内，3个基因是特别感兴趣的ITGB 8、HDAC 9和TWIST 1。此外，在EGFR突变的肿瘤中鉴定了CDKN 2A的纯合缺失和RB 1的洛。因此，我们在一个更大的肿瘤系列中检测EGFR突变、CDKN 2A纯合性缺失和细胞周期蛋白扩增之间是否存在联系。事实上，在一系列非小细胞肺癌（n = 98）中，我们发现CDKN 2A纯合缺失与EGFR突变和不吸烟有关，而细胞周期蛋白扩增（CCNE 1和CCND 1）与TP 53突变和吸烟习惯有关。总之，我们的结果表明，EGFR和KRAS突变的肺ADC之间的基因组范围的改变模式不同，描述了两种致癌合作模型，涉及EGFR突变和CDKN 2A缺失或细胞周期蛋白扩增和TP 53失活突变，并确定了与肺癌中EGFR突变相关的7 p和14 q处的新染色体区域。
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. 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. 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.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
影响因子：
3.4
作者：
Bondi, J;Husdal, A;Bukholm, IRK
通讯作者：
Bukholm, IRK
影响因子：
8.8
作者：
Mishina, T;Dosaka-Akita, H;Kawakami, Y
通讯作者：
Kawakami, Y
影响因子：
45.3
作者：
Wakelee, Heather A.;Chang, Ellen T.;West, Dee W.
通讯作者：
West, Dee W.
影响因子：
5.7
作者：
Shibata, Tatsuhiro;Hanada, Satoko;Hirohashi, Setsuo
通讯作者：
Hirohashi, Setsuo