The role of LKB1 in lung cancer
The role of LKB1 in lung cancer
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DOI：
10.1007/s10689-011-9443-0
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发表时间：
2011-09-01
期刊：
影响因子：
2.2
通讯作者：
Sanchez-Cespedes, Montse
中科院分区：
文献类型：
--
作者：
Sanchez-Cespedes, Montse
在人类中，LKB1基因位于19号染色体的短臂上，该基因在肺癌中经常缺失。与大多数散发性癌症不同，在非小细胞肺癌(NSCLC)中，近一半的肿瘤含有LKB1的体细胞和纯合子失活突变。在NSCLC中，LKB1失活主要发生在吸烟者的腺癌中，并与其他重要癌症基因的突变共存，包括KRAS和TP53。值得注意的是，LKB1的改变经常与另一个重要的肿瘤抑制基因BRG1(也称为SMARCA4)的失活同时发生，该基因也位于染色体19p上。本文综述了LKB1基因突变在肺癌中的频率和模式，以及LKB1蛋白参与肺癌发生发展的不同生物学途径。最后，讨论了LKB1缺失在癌症治疗，特别是肺癌治疗中的可能的临床应用。
In humans, the LKB1 gene is located on the short arm of chromosome 19, which is frequently deleted in lung tumors. Unlike most cancers of sporadic origin, in non-small cell lung cancer (NSCLC) nearly half of the tumors harbor somatic and homozygous inactivating mutations in LKB1. In NSCLC, LKB1 inactivation strongly predominates in adenocarcinomas from smokers and coexists with mutations at other important cancer genes, including KRAS and TP53. Remarkably, LKB1 alterations frequently occur simultaneously with inactivation at another important tumor suppressor gene, BRG1 (also called SMARCA4), which is also located on chromosome 19p. The present review considers the frequency and pattern of LKB1 mutations in lung cancer and the distinct biological pathways in which the LKB1 protein is involved in the development of this type of cancer. Finally, the possible clinical applications in cancer management, especially in lung cancer treatment, associated with the presence of absence of LKB1 are discussed.