期刊
JOURNAL OF THORACIC ONCOLOGY
卷 6, 期 9, 页码 1594-1598出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/JTO.0b013e3182217d81
关键词
Non-small cell lung cancer; miR-101; Deletion
资金
- Michael Smith Foundation for Health Research
- Vanier Canada Graduate Scholarship
- Canadian Institutes for Health Research (CIHR) [MOP 86731, MOP 94867]
- Canadian Cancer Society [CCS20485]
- NCI Early Detection Research Network (EDRN) [5U01 CA84971-10]
- Canary Foundation
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.
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