Spectrum of LKB1, EGFR, and KRAS mutations in chinese lung adenocarcinomas.
Spectrum of LKB1, EGFR, and KRAS mutations in chinese lung adenocarcinomas.
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中国肺腺癌中 LKB1、EGFR 和 KRAS 突变谱
DOI：
10.1097/jto.0b013e3181e05016
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发表时间：
2010-08
期刊：
影响因子：
--
通讯作者：
Ji H
中科院分区：
文献类型：
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作者：
Gao B;Sun Y;Zhang J;Ren Y;Fang R;Han X;Shen L;Liu XY;Pao W;Chen H;Ji H
简介：体细胞LKB 1突变在高加索人和东亚（日本和韩国）人群中以不同的频率在肺腺癌中发现。本研究旨在描述中国患者中LKB 1突变的频率、其与EGFR和KRAS突变的关系及其相关临床病理特征。研究方法：从2007年10月至2009年7月连续收集的239例肺腺癌被解剖成3至4个小块（3 mm），用于肿瘤内容物的组织病理学分析。使用来自86份肿瘤含量超过70%的样本的基因组DNA和/或cDNA对LKB 1（外显子1-9）、EGFR（外显子18-21）和KRAS（外显子2）进行测序。LKB 1种系突变状态通过对来自组织学上正常的匹配的组织学上远距离的肺组织的基因组DNA进行测序来确定。结果：6.9%的肺腺癌携带LKB 1体细胞突变。共有10.5%的患者具有LKB 1生殖系多态性F354 L。有趣的是，在这些患者中的两个中，肿瘤显示该等位基因的杂合性丢失。EGFR激酶结构域和KRAS突变分别在66.3%和2.3%的中国人肺腺癌中发现。在1例患者中观察到同时发生LKB 1和EGFR体细胞突变。两种KRAS突变型肿瘤均携带LKB 1突变。结论：这些数据提供了重要的临床和分子特征的肺腺癌从中国患者。
Introduction: Somatic LKB1 mutations are found in lung adenocarcinomas at different frequencies in Caucasian and East Asian (Japanese and Korean) populations. This study was designed to characterize the frequency of LKB1 mutations, their relationship to EGFR and KRAS mutations, and their associated clinicopathologic characteristics in Chinese patients. Methods: Two hundred thirty-nine lung adenocarcinomas consecutively collected from October 2007 to July 2009 were dissected into 3 to 4 small (3 mm) pieces for histopathological analyses of tumor content. Genomic DNA and/or cDNA from 86 samples with more than 70% tumor content were used for sequencing of LKB1 (exons 1–9), EGFR (exons 18–21), and KRAS (exon 2). LKB1 germline mutation status was determined by sequencing of genomic DNA from matched histologically distant lung tissues that are histologically normal. Results: 6.9% of lung adenocarcinomas harbored LKB1 somatic mutations. A total of 10.5% of patients had an LKB1 germline polymorphism, F354L. Interestingly, in two of these patients, tumors displayed loss of heterozygosity at this allele. EGFR kinase domain and KRAS mutations were found in 66.3% and 2.3% of Chinese lung adenocarcinomas, respectively. Concurrent LKB1 and EGFR somatic mutations were observed in one patient. Both KRAS-mutant tumors harbored LKB1 mutations. Conclusions: These data provide important clinical and molecular characteristics of lung adenocarcinomas from Chinese patients.