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LKB1/STK11失活在肺腺癌中是常见事件。

Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung.

作者信息

Sanchez-Cespedes Montserrat, Parrella Paola, Esteller Manel, Nomoto Shuji, Trink Barry, Engles James M, Westra William H, Herman James G, Sidransky David

机构信息

Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.

出版信息

Cancer Res. 2002 Jul 1;62(13):3659-62.

Abstract

Frequent losses of chromosome 19p have recently been observed in sporadic lung adenocarcinomas, targeting the location of a critical tumor suppressor gene. Here we performed fine mapping of the short arm of chromosome 19 and found that the LKB1/STK11 gene mapped in the minimal-deleted region. Because germ-line mutations at LKB1/STK11 result in the Peutz-Jeghers syndrome and an increased risk of cancer, we performed a detailed genetic screen of the LKB1/STK11 gene in lung tumors. We detected a high frequency of somatic alterations (mainly nonsense mutations) in primary lung adenocarcinomas and in lung cancer cell lines. Thus, our findings demonstrate for the first time that LKB1/STK11 inactivation is a very common event and may be integrally involved in the development of sporadic lung adenocarcinoma.

摘要

最近在散发性肺腺癌中观察到19号染色体短臂频繁缺失,该区域正是一个关键肿瘤抑制基因所在位置。在此,我们对19号染色体短臂进行了精细定位,发现LKB1/STK11基因定位于最小缺失区域。由于LKB1/STK11基因的种系突变会导致黑斑息肉综合征并增加患癌风险,我们对肺肿瘤中的LKB1/STK11基因进行了详细的遗传学筛查。我们在原发性肺腺癌和肺癌细胞系中检测到高频的体细胞改变(主要为无义突变)。因此,我们的研究结果首次证明LKB1/STK11失活是一个非常常见的事件,可能在散发性肺腺癌的发生发展中起着不可或缺的作用。

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