期刊
CLINICAL CANCER RESEARCH
卷 14, 期 20, 页码 6618-6624出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-08-1018
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资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Japan Society
- Ministry of Health, Labor, and Welfare of Japan
- National Institute of Biomedical Innovation
- Smoking Research Foundation
- Vehicle Racing Commemorative Foundation
Purpose: EML4-ALK is a fusion-type protein tyrosine kinase that is generated by inv(2) (p21p23) in the genome of non - small cell lung cancer (NSCLC). To allow sensitive detection of EML4-ALK fusion transcripts, we have now developed a multiplex reverse transcription-PCR (RT-PCR) system that captures all in-frame fusions between the two genes. Experimental Design: Primers were designed to detect all possible in-frame fusions of EML4 to exon 20 of ALK, and a single-tube multiplex RT-PCR assay was done with total RNA from 656 solid tumors of the lung (n = 364) and 10 other organs. Results: From consecutive lung adenocarcinoma cases (n = 253), we identified 11 specimens (4.35%) positive for fusion transcripts, 9 of which were positive for the previously identified variants 1, 2, and 3. The remaining two specimens harbored novel transcript isoforms in which exon 14 (variant 4) or exon 2 (variant 5) of EML4 was connected to exon 20 of ALK. No fusion transcripts were detected for other types of lung cancer (n = 111) or for tumors from 10 other organs (n = 292). Genomic rearrangements responsible for the fusion events in NSCLC cells were confirmed by genomic PCR analysis and fluorescence in situ hybridization. The novel isoforms of EML4-ALK manifested marked oncogenic activity, and they yielded a pattern of cytoplasmic staining with fine granular foci in immunohistochemical analysis of NSCLC specimens. Conclusions: These data reinforce the importance of accurate diagnosis of EML4-ALK - positive tumors for the optimization of treatment strategies.
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