Prevalence and specificity of LKB1 genetic alterations in lung cancers
Prevalence and specificity of LKB1 genetic alterations in lung cancers
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DOI：
10.1038/sj.onc.1210418
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发表时间：
2007-08-30
期刊：
影响因子：
8
通讯作者：
Yokota, J.
中科院分区：
文献类型：
--
作者：
Matsumoto, S.;Iwakawa, R.;Yokota, J.
种系LKB1突变导致Peutz-Jeghers综合征，这是一种遗传性疾病，易患胃肠道错构瘤性息肉病和几种恶性肿瘤。体细胞LKB1改变在散发性癌症中是罕见的，然而，一些报告显示在相当一部分肺癌中存在体细胞改变。为了确定LKB1基因改变在肺癌中的普遍性和特异性，我们对大量肺癌细胞系和肺腺癌（AdC）标本进行了检测。LKB1基因改变在细胞系中经常被检测到（21/ 70,30 %），特别是在非小细胞肺癌（nsclc）中（20/ 51,39 %），并且在KRAS突变的细胞系中更常见。点突变仅在adc和大细胞癌中检测到，而纯合缺失在所有组织学类型的肺癌中都检测到。在肺AdC标本中，91名男性吸烟者中有7名（8%）发现LKB1突变，但64名女性和/或不吸烟者中没有发现LKB1突变，并且在低分化肿瘤中更为常见。细胞系和肿瘤标本之间LKB1改变频率的差异可能是由于肿瘤标本中非癌细胞的污染掩盖了缺失。这些结果表明，体细胞LKB1遗传改变优先发生在低分化的肺adc亚群中，这似乎与吸烟男性有关。
Germline LKB1 mutations cause Peutz-Jeghers syndrome, a hereditary disorder that predisposes to gastrointestinal hamartomatous polyposis and several types of malignant tumors. Somatic LKB1 alterations are rare in sporadic cancers, however, a few reports showed the presence of somatic alterations in a considerable fraction of lung cancers. To determine the prevalence and the specificity of LKB1 alterations in lung cancers, we examined a large number of lung cancer cell lines and lung adenocarcinoma ( AdC) specimens for the alterations. LKB1 genetic alterations were frequently detected in the cell lines ( 21/70, 30%), especially in non-small cell lung cancers ( NSCLCs) ( 20/51, 39%), and were significantly more frequent in cell lines with KRAS mutations. Point mutations were detected only in AdCs and large cell carcinomas, whereas homozygous deletions were detected in all histological types of lung cancer. Among lung AdC specimens, LKB1 mutations were found in seven ( 8%) of 91 male smokers but in none of 64 females and/or nonsmokers, and were significantly more frequent in poorly differentiated tumors. The difference in the frequency of LKB1 alterations between cell lines and tumor specimens was likely to be owing to masking of deletions by the contamination of noncancerous cells in the tumor specimens. These results indicate that somatic LKB1 genetic alterations preferentially occur in a subset of poorly differentiated lung AdCs that appear to correlate with smoking males.