The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
Identification of Novel Isoforms of the EML4-ALK Transforming Gene in Non–Small Cell Lung Cancer
Abstract
The genome of a subset of non–small-cell lung cancers (NSCLC) harbors a small inversion within chromosome 2 that gives rise to a transforming fusion gene, EML4-ALK, which encodes an activated protein tyrosine kinase. Although breakpoints within EML4 have been identified in introns 13 and 20, giving rise to variants 1 and 2, respectively, of EML4-ALK, it has remained unclear whether other isoforms of the fusion gene are present in NSCLC cells. We have now screened NSCLC specimens for other in-frame fusion cDNAs that contain both EML4 and ALK sequences. Two slightly different fusion cDNAs in which exon 6 of EML4 was joined to exon 20 of ALK were each identified in two individuals of the cohort. Whereas one cDNA contained only exons 1 to 6 of EML4 (variant 3a), the other also contained an additional 33-bp sequence derived from intron 6 of EML4 (variant 3b). The protein encoded by the latter cDNA thus contained an insertion of 11 amino acids between the EML4 and ALK sequences of that encoded by the former. Both variants 3a and 3b of EML4-ALK exhibited marked transforming activity in vitro as well as oncogenic activity in vivo. A lung cancer cell line expressing endogenous variant 3 of EML4-ALK underwent cell death on exposure to a specific inhibitor of ALK catalytic activity. These data increase the frequency of EML4-ALK–positive NSCLC tumors and bolster the clinical relevance of this oncogenic kinase. [Cancer Res 2008;68(13):4971–6]
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Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer
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RET, ROS1 and ALK fusions in lung cancer
Takeuchi, K., Soda, M., Togashi, Y., Suzuki, R., Sakata, S., Hatano, S., Asaka, R., Hamanaka, W., Ninomiya, H., Uehara, H., et al. (2012) · Nature Medicine · doi:10.1038/nm.2658 · Cited by 1,320
Self-citationHaplotyping germline and cancer genomes with high-throughput linked-read sequencing
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In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system
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The biology and treatment of EML4-ALK non-small cell lung cancer
Sasaki, T., Rodig, S. J., Chirieac, L. R., & Jänne, P. A. (2010) · European Journal of Cancer · doi:10.1016/j.ejca.2010.04.002 · Cited by 555
Genetic alterations defining NSCLC subtypes and their therapeutic implications
Pikor, L. A., Ramnarine, V. R., Lam, S., & Lam, W. L. (2013) · Lung Cancer · doi:10.1016/j.lungcan.2013.07.025 · Cited by 375
Metadata
- Authors
- Choi, Y. L., Takeuchi, K., Soda, M., Inamura, K., Togashi, Y., Hatano, S., Enomoto, M., Hamada, T., Haruta, H., Watanabe, H., Kurashina, K., Hatanaka, H., Ueno, T., Takada, S., Yamashita, Y., Sugiyama, Y., Ishikawa, Y., & Mano, H.
- Venue
- Cancer Research
- Published
- 2008-07-01
- Volume
- 68
- Issue
- 13
- Pages
- 4971-4976
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2031159738
- Cited by
- 438
- References
- 19
- FWCI
- 25.60
- Type
- journal article
- Language
- en
- Open access
- closed
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- Choi, Y. L., Takeuchi, K., Soda, M., Inamura, K., Togashi, Y., Hatano, S., Enomoto, M., Hamada, T., Haruta, H., Watanabe, H., Kurashina, K., Hatanaka, H., Ueno, T., Takada, S., Yamashita, Y., Sugiyama, Y., Ishikawa, Y., & Mano, H. (2008). Identification of Novel Isoforms of the EML4-ALK Transforming Gene in Non–Small Cell Lung Cancer. Cancer Research. https://doi.org/10.1158/0008-5472.can-07-6158
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