Loss of MKK3 and MK2 Copy Numbers in Non-Small Cell Lung Cancer.
Loss of MKK3 and MK2 Copy Numbers in Non-Small Cell Lung Cancer.
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DOI：
10.7150/jca.13651
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发表时间：
2016
影响因子：
3.9
通讯作者：
Zienolddiny S
中科院分区：
文献类型：
--
作者：
Samulin Erdem J;Skaug V;Haugen A;Zienolddiny S
鉴定p38丝裂原活化蛋白激酶（MAPK）通路成员的遗传改变是重要的，因为这些蛋白质在肿瘤进展中具有动态作用，并且可以作为癌症的潜在治疗靶点。我们分析了233例非小细胞肺癌（NSCLC）患者的肿瘤和非肿瘤肺组织中MAPK激酶3（MKK 3）和MAPK激活激酶2（MK2）基因的拷贝数改变（CNA）。我们报告了NSCLC中MKK 3和MK2基因的常见CNA。在31%的NSCLC肿瘤中检测到MKK 3基因的拷贝数丢失（比值比：7.08，95%置信区间：3.2-15.6，P<0.001），在28%的肿瘤中检测到MK2基因的拷贝数丢失（比值比：3.68，95%置信区间：1.9-7.2，P<0.001）。一些非肿瘤组织显示MKK 3拷贝数升高，在89%的配对肿瘤中同时丢失。MKK 3基因缺失在鳞状细胞癌和大细胞癌中的发生率明显高于腺癌。这些数据证明了NSCLC肿瘤中MKK 3和MK2基因组拷贝数的新丢失，并表明这些基因是NSCLC中令人感兴趣的治疗候选基因。
Identification of genetic alterations in members of the p38 mitogen-activated protein kinase (MAPK) pathway is important as these proteins have dynamic roles in tumor progression and may serve as potential therapeutic targets in cancer. We analyzed tumor and non-tumorous lung tissue of 233 non-small cell lung cancer (NSCLC) patients for the presence of copy number alterations (CNAs) in the MAPK kinase 3 (MKK3) and MAPK-activated kinase 2 (MK2) genes. We report frequent CNAs in MKK3 and MK2 genes in NSCLC. Copy number losses were detected in 31% of NSCLC tumors (odds ratio: 7.08, 95% confidence interval: 3.2-15.6, P<0.001) for the MKK3 gene and in 28% of tumors for the MK2 gene (odds ratio: 3.68, 95% confidence interval: 1.9-7.2, P<0.001). Several of the non-tumorous tissues showed an elevated MKK3 copy number, with a concurrent loss of this in 89% of the paired tumors. MKK3 gene deletions were significantly more frequent in squamous and large cell carcinoma than in adenocarcinoma. These data demonstrate a novel loss of MKK3 and MK2 genomic copy numbers in NSCLC tumors, and suggest these genes as interesting therapeutic candidates in NSCLC.