PTEN mutations and relationship to EGFR, ERBB2, KRAS, and TP53 mutations in non-small cell lung cancers
PTEN mutations and relationship to EGFR, ERBB2, KRAS, and TP53 mutations in non-small cell lung cancers
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DOI：
10.1016/j.lungcan.2009.11.012
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发表时间：
2010-09-01
期刊：
影响因子：
5.3
通讯作者：
Park, Jae Yong
中科院分区：
文献类型：
--
作者：
Jin, Guang;Kim, Min Jung;Park, Jae Yong
在非小细胞肺癌（NSCLCs）中，第10号染色体上缺失的磷酸酶和张力蛋白同源物（PTEN）的体细胞突变已在少数病例中进行了研究。此外，尚未研究PTEN突变与表皮生长因子受体（埃格）、KRAS和TP 53突变之间的关系。因此，我们调查了176例手术切除的NSCLC中PTEN突变的频率，并分析了PTEN突变与EGFR、ERBB 2、KRAS和TP 53突变之间的关系。通过聚合酶链反应和直接测序确定PTEN（外显子1-9）、EGFR（外显子18-21）、ERBB 2（外显子19和20）、KRA 5（外显子1）和TP 53（外显子2-11）的突变。176例肿瘤中有8例（4.5%）存在PTEN突变。PTEN基因突变仅见于吸烟者，且在鳞状细胞癌中的发生率明显高于腺癌（10.2%vs1.7%，P = 0.02）。EGFR、ERBB 2、KRAS和TP 53基因突变分别为36例（20.5%）、2例（1.1%）、11例（6.3%）和66例（37.5%）。在8例PTEN突变的肿瘤中，1例同时存在EGFR突变，4例同时存在TP 53突变。而在KRA 5突变的肿瘤中未发现PTEN突变。我们的研究结果表明，PTEN突变在NSCLC中相对常见，因此分析PTEN突变可能有助于全面了解EGFR信号通路相关的遗传改变。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
Somatic mutations of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in non-small cell lung cancers (NSCLCs) have been investigated in but a small number of cases. In addition, the relationship between PTEN mutations and epidermal growth factor receptor (EGER), KRAS, and TP53 mutations has not been investigated. Therefore, we investigated the frequency of PTEN mutations in 176 surgically resected NSCLCs and analyzed the relationship between PTEN mutations and EGFR, ERBB2, KRAS, and TP53 mutations. Mutations of PTEN (exons 1-9), EGFR (exons 18-21), ERBB2 (exons 19 and 20), KRA5 (exon 1), and TP53 (exons 2-11) were determined by polymerase chain reaction and direct sequencing. PTEN mutations were present in 8 (4.5%) of the 176 tumors. PTEN mutations were only found in ever-smokers and were significantly more frequent in squamous cell carcinoma than in adenocarcinoma (10.2% vs 1.7%, P = 0.02). mutations of EGFR, ERBB2, KRAS, and TP53 genes were found in 36 (20.5%), 2 (1.1%), 11 (6.3%), and 66 (37.5%) cases, respectively. Of the 8 tumors with PTEN mutations, 1 case concurrently had an EGFR mutation and 4 cases had TP53 mutations. However, PTEN mutations were not found in the tumors with KRA5 mutation. Our findings indicate that PTEN mutations are relatively common in NSCLC, and thus analysis of PTEN mutations may facilitate a comprehensive understanding of the genetic alterations related to the EGFR signaling pathway. (C) 2009 Elsevier Ireland Ltd. All rights reserved.