miR-101 DNA Copy Loss is a Prominent Subtype Specific Event in Lung Cancer
miR-101 DNA Copy Loss is a Prominent Subtype Specific Event in Lung Cancer
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DOI：
10.1097/jto.0b013e3182217d81
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发表时间：
2011-09-01
影响因子：
20.4
通讯作者：
Lam, Wan L.
中科院分区：
文献类型：
--
作者：
Thu, Kelsie L.;Chari, Raj;Lam, Wan L.
简介：MicroRNA-101 （miR-101）在癌症中经常下调，并表现出抗肿瘤特性，这表明miR-101可能是一种肿瘤抑制因子。miR-101在人类基因组中的两个位点编码：1p31.3 （miR-101-1）和9p24.1 （miR-101-2）。我们试图研究肺癌主要亚型中miR-101位点特异性缺失和基因组丢失。方法：分析高分辨率阵列比较基因组杂交和单核苷酸多态性阵列数据，确定miR-101-1和miR-101-2在7个独立队列中的DNA拷贝数状态和缺失边界，这些队列包括1236例肺癌样本和20例肺癌原位样本。miR-101在肺癌细胞系和肿瘤中的表达也被研究。结果：在分析的29%的肺癌中发现了任一基因组位点的miR-101缺失，并与miR-101表达降低相关。与小细胞肺癌相比，9p位点的缺失更常见，在非小细胞肺癌中更常见。原位肺癌也存在miR-101缺失，这表明基因组丢失可能是肺癌发展的早期事件。最后，在一些情况下，miR-101在9p上的缺失不包括CDKN2A的缺失，这提供了证据表明miR-101的缺失不仅仅是CDKN2A缺失的乘客。结论：miR-101基因组丢失在非小细胞肺癌中经常发生，可能是肺肿瘤发生的早期事件。DNA缺失可能是miR-101在非小细胞肺癌中下调的一个重要分子机制，而不是在小细胞肺癌中。
Introduction: MicroRNA-101 (miR-101) is frequently downregulated in cancer and exhibits antitumorigenic properties, suggesting that miR-101 is a putative tumor suppressor. miR-101 is encoded at two loci in the human genome: 1p31.3 (miR-101-1) and 9p24.1 (miR-101-2). We sought to investigate miR-101 locus-specific deletions and genomic loss in the major subtypes of lung cancer.Methods: Analyses of high-resolution array comparative genomic hybridization and single-nucleotide polymorphism array data were performed to determine the DNA copy number status and deletion boundaries of miR-101-1 and miR-101-2 in seven independent cohorts that comprised 1236 lung cancer specimens and 20 lung carcinoma in situ samples. miR-101 expression was also investigated in lung cancer cell lines and tumors.Results: miR-101 loss at either genomic locus was identified in 29% of lung cancers analyzed and was associated with reduced miR-101 expression. Loss was more frequent at the 9p locus and occurred more often in NSCLC as opposed to small cell lung cancer. Lung carcinoma in situ also harbored miR-101 deletions, suggesting that genomic loss may be an early event in lung cancer development. Finally, miR-101 deletions on 9p were exclusive of CDKN2A deletions in several cases, providing evidence that loss of miR-101 is not merely a passenger of CDKN2A deletion.Conclusions: miR-101 genomic loss occurs frequently in NSCLC and may be an early event in lung tumorigenesis. DNA deletions likely represent a prominent molecular mechanism of miR-101 downregulation in NSCLC but not in small cell lung cancer.