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Better Selection Model for EML4-ALK Fusion Gene Test in Patients with Non-Small-Cell Lung Cancer

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DOI: 10.4236/jct.2013.48A009    3,055 Downloads   4,469 Views   Citations


Background: In the last decade, the search for gene mutations in lung cancer has been constantly growing. EGFR, KRAS mutations and, recently, the EML4-ALK fusion can guide the selection of treatment for patients who carry a specific mutation. Methods: During 2010-2011, EML4-ALK fusion test has been performed in Israel, mostly for wild type EGFR non-squamous NSCLC patients based on fluorescent in-situ hybridization (FISH) technique to detect EML4-ALK rearrangements. Results: Between January 2010 and December 2011, 3341 patients were diagnosed with lung cancer in Israel. Of the 2997 patients with NSCLC 687 had squamous cell carcinoma and 2310 had non-squamous NSCLC. This study focused on available 125 non-squamous NSCLC cases in which analysis for EML4-ALK rearrangement was available. All were negative for EGFR mutation. Nineteen (15.2%) were found positive for the fusion, a figure 2 - 10 times higher compared with previously reported findings. The EML4-ALK fusion was significantly more prevalent in younger male patients (52.1 vs. 61.3 years, p = 0.049), in whom every additional year reduced the chance to find the fusion by 7% [CI = 0.93 (0.88 - 0.99), p = 0.03]. Conclusions: A stepwise approach based on histology and prior EGFR analysis to detect EML4-ALK fusion is highly efficient with a related increased yield of detection. We recommend testing patients with non-squamous cell lung carcinoma after ruling out an EGFR mutation. The chance to find the ALK fusion is significantly greater in younger men.

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The authors declare no conflicts of interest.

Cite this paper

Shlomi, D. , Onn, A. , Gottfried, M. , Bar, J. , Biran, H. , Ilouze, M. , Dvir, A. , Nechushtan, H. , Soussan-Gutman, L. and Peled, N. (2013) Better Selection Model for EML4-ALK Fusion Gene Test in Patients with Non-Small-Cell Lung Cancer. Journal of Cancer Therapy, 4, 54-58. doi: 10.4236/jct.2013.48A009.


[1] T. J. Lynch, D. W. Bell, R. Sordella, et al., “Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non-Small-Cell Lung Cancer to Gefitinib,” New England Journal of Medicine, Vol. 350, No. 21, 2004, pp. 2129-2139.
[2] F. A. Shepherd, J. R. Pereira, T. Ciuleanu, E. H. Tan, V. Hirsh, S. Thongprasert, et al., “Erlotinib in Previously Treated Non-Small-Cell Lung Cancer,” New England Journal of Medicine, Vol. 353, 2005, pp. 123-132. doi:10.1056/NEJMoa050753
[3] M. Soda, Y. L. Choi, M. Enomoto, et al., “Identification of the Transforming EML4-ALK Fusion Gene in NonSmall-Cell Lung Cancer,” Nature, Vol. 448, No. 7153, 2007, pp. 561-566.
[4] M. Shiota, S. Nakamura, R. Ichinohasama, et al., “Anaplastic Large Cell Lymphomas Expressing the Novel Chimeric Protein p80NPM/ALK: A Distinct Clinicopathologic Entity,” Blood, Vol. 86, No. 5, 1995, pp. 1954-1960.
[5] J. Cools, I. Wlodarska, R. Somers, et al., “Identification of Novel Fusion Partners of ALK, the Anaplastic Lymphoma Kinase, in Anaplastic Large-Cell Lymphoma and Inflammatory Myofibroblastic Tumour,” Genes Chromosomes Cancer, Vol. 34, No. 4, 2002, pp. 354-362.
[6] K. Inamura, K. Takeuchi, Y. Togashi, et al., “EML4-ALK Fusion Is Linked to Histological Characteristics in a Subset of Lung Cancers,” Journal of Thoracic Oncology, Vol. 3, No. 1, 2008, pp. 13-17.
[7] K. Inamura, K. Takeuchi, Y. Togashi, et al., “EML4-ALK Lung Cancers Are Characterized by Rare Other Mutations, a TTF-1 Cell Lineage, an Acinar Histology, and Young Onset,” Modern Pathology, Vol. 22, No. 4, 2009, pp. 508-515. doi:10.1038/modpathol.2009.2
[8] D. W. Wong, E. L. Leung, K. K. So, et al., “The EML4-ALK Fusion Gene Is Involved in Various Histologic Types of Lung Cancers from Non-Smokers with Wild-Type EGFR and KRAS,” Cancer, Vol. 115, No. 8, 2009, pp. 1723-1733. doi:10.1002/cncr.24181
[9] A. T. Shaw, B. Y. Yeap, M. Mino-Kenudson, et al., “Clinical Features and Outcome of Patients with NonSmall-Cell Lung Cancer Who Harbor EML4-ALK,” Journal of Clinical Oncology, Vol. 27, No. 26, 2009, pp. 4247-4253. doi:10.1200/JCO.2009.22.6993
[10] T. Takahashi, M. Sonobe, M. Kobayashi, et al., “Clinicopathologic Features of Non-Small-Cell Lung Cancer with EML4-ALK Fusion Gene,” Annals of Surgical Oncology, Vol. 17, No. 3, 2010, pp. 889-897.
[11] A. T. Shaw, B. Y. Yeap, B. J. Solomon, et al., “Effect of Crizotinib on Overall Survival in Patients with Advanced Non-Small-Cell Lung Cancer Harbouring ALK Gene Rearrangement: A Retrospective Analysis,” Lancet Oncology, Vol. 12, No. 11, 2011, pp. 1004-1012.
[12] R Development Core Team, “R: A Language and Environment for Statistical Computing,” R Foundation for Statistical Computing, Vienna, 2006.
[13] H. Shigematsu, L. Lin, T. Takahashi, et al., “Clinical and Biological Features Associated with Epidermal Growth Factor Receptor Gene Mutations in Lung Cancers,” Journal of the National Cancer Institute, Vol. 97, No. 5, 2005, pp. 339-346. doi:10.1093/jnci/dji055
[14] R. Rosell, T. Moran, C. Queralt, et al., “Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer,” New England Journal of Medicine, Vol. 361, 2009, pp. 958-967. doi:10.1056/ NEJMoa0904554
[15] M. P. Martelli, G. Sozzi, L. Hernandez, et al., “EML4-ALK Rearrangement in Non-Small-Cell Lung Cancer and Non-Tumor Lung Tissues,” American Journal of Pathology, Vol. 174, No. 2, 2009, pp. 661-670.
[16] J. P. Koivunen, C. Mermel, C. Murphy, et al., “EML4-ALK Fusion Gene and Efficacy of an ALK Kinase Inhibitor in Lung Cancer,” Clinical Cancer Research, Vol. 14, No. 13, 2008, pp. 4275-4283.
[17] S. J. Rodig, M. Mino-Kenudson, S. Dacic, et al., “Unique Clinicopathologic Features Characterize ALK-Rearranged Lung Adenocarcinoma in the Western Population,” Clinical Cancer Research, Vol. 15, No. 16, 2009, pp. 5216-5223.

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