What are the uncommon Anaplastic Lymphoma Kinase (ALK) fusions in non-small cell lung cancer?
The lung cancer carcinogenesis is increasingly related to genetic disorders that lead to use specific targeted therapies which improve clinical outcome and survival. Gene fusion is one of the mechanisms of lung cancer pathogenesis besides gene mutation. The oncogenic echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene was the first described in non small cell lung cancer (NSCLC) and it’s the most frequent ALK rearrangement which occurs in approximately 5% of NSCLC. The development of sequencing technology has allowed the discovery of other ALK partners that cause an ALK fusion in NSCLC. They are still less known, however. The aim of this revue is to report the novel ALK fusions in NSCLC described in the literature and their particular characteristics. We will present the kinesin family member 5B (KIF5B) - ALK fusion, the huntingtin interacting protein 1 (HIP 1)- ALK fusion, and other uncommon ALK fusions.
Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007;448:561-566.
Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N ENGL J MED 2014; 371:2167-2177.
Takeuchi K, Choi YL, Togashi Y, et al. KIF5B, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer. Clin Cancer Res 2009; 15:3143-3149.
Wong D, Leung E, Wong S, et al. A Novel KIF5B-ALK variant in nonsmall cell lung cancer. Cancer 2011;15:2709-2718.
Kimura H, Nakajima T, Takeuchi K, et al. ALK fusion gene positive lung cancer and 3 cases treated with an inhibitor for ALK kinase activity. Lung Cancer 2012;75:66-72.
Wang R, Pan Y, Li C, et al. The use of quantitative real-time reverse transcriptase PCR for 5' and 3' portions of ALK transcripts to detect ALK rearrangements in lung cancers. Clin Cancer Res 2012;18: 4725-4732.
Wang Q, Yang X, He Y, et al. droplet digital PCR for absolute quantification of EML4-ALK gene rearrangement in lung adenocarcinoma. The Journal of Molecular Diagnostics 2015; 17:515-520.
Kwak El, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363: 1693-1703.
Hong M, Kim RN, Song JY, et al. HIP 1-ALK, a novel fusion protein identified in lung adenocarcinoma. Journal of Thoracic Oncology 2014;419-422.
Fang D, Zhang B, Gu Q, et al. HIP 1-ALK, a novel alk fusion variant that responds to crizotinib. Journal of Thoracic Oncology 2014 ;9 :285-294.
Ou SI, Klempner SJ, Greenbowe JR, et al. Identification of a novel HIP 1-ALK fusion variant in non-small-cell lung cancer and discovery of ALK I1171 mutations in two ALK-rearranged NSCLC patients with resistance to Alectinib. Journal of Thoracic Oncology 2014;9:1821-1825.
Togashi Y, Soda M, Sakata S, et al. KLC1-ALK :a novel fusion in lung cancer identified using a formalin fixed paraffin embedded tissue only. Plos ONE 2012;7:e31323.
Choi YL, Lira ME, Hong M, et al. A novel fusion of TPR and ALK in lung adenocarcinoma. Journal of Thoracic Oncology 2014;9:563-566.
Shan L, Jiang P, Xu F, et al.BIRC6-ALK, a novel fusion gene in ALK break-apart FISH-negative lung adenocarcinoma, responds to crizotinib. Journal of Thoracic Oncology 2015;10:37-39.
Kim RN, Choi YL, Lee MS, et al. SEC31A-ALK fusion gene in lung adenocarcinoma.Cancer Res Treat 2016;48:398-402.
Gu FF, Zhang Y, Liu YY, et al. Lung adenocarcinoma harboring concomittant SPTBN1-ALK fusion, c-Met overexpression and HER-2 amplification with inherent resistance to crizotinib chemotherapy and radiotherapy. Journal of Hematology and Oncology 2016;9:66.
Rivoka K, Guo A, Zeng Q, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 2007;131:1190-1203.
Jung Y, Kim P, Keum J, et al. Discovery of ALK-PTPN3 gene fusion from human non-small-cell lung carcinoma cell line using next generation RNA sequencing. Genes Chromosomes Cancer 2012;51:590-597.
Ou SH, Bartlett CH, Mino-Kinudson M, et al. Crizotinib for the treatment of ALK-rearranged non-small cell lung cancer :a success story to usher in the second decade of molecular targeted therapy in oncology. Oncologist 2012;17:351-1375.
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