OFCC1-ALK (Ointergenic: A20): A novel OFCC1 intergenic region-ALK fusion identified from a lung adenocarcinoma patient

Anaplastic lymphoma kinase (ALK) gene rearrangements, appearing in 5 %–7 % lung adenocarcinomas, are promising driving oncogenes in NSCLC for dramatic response to ALK tyrosine kinase inhibitor (ALK-TKI) [ [1] Hirsch F.R. Suda K. Wiens J. Bunn Jr., P.A. New and emerging targeted treatments in advanced non-small-cell lung cancer. Lancet. 2016; 388: 1012-1024 Abstract Full Text Full Text PDF PubMed Scopus (254) Google Scholar , [2] Solomon B.J. Mok T. Kim D.-W. Wu Y.-L. Nakagawa K. Mekhail T. et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N. Engl. J. Med. 2014; 371: 2167-2177 Crossref PubMed Scopus (2076) Google Scholar ]. With the development of next generation sequence (NGS), a number of subtypes of ALK fusions were detected in recent years. In addition to the most common and classical rearrangement of echinoderm microtubule associated protein like 4 gene (EML4) and ALK, it harbors the 5’ end of EML4 fused to the entire ALK kinase domain and results in constitutive kinase activation [ [1] Hirsch F.R. Suda K. Wiens J. Bunn Jr., P.A. New and emerging targeted treatments in advanced non-small-cell lung cancer. Lancet. 2016; 388: 1012-1024 Abstract Full Text Full Text PDF PubMed Scopus (254) Google Scholar ]. To date, at least 90 distinct non-EML4 ALK fusion partners have been identified in ALK + NSCLC. Furthermore, 28 potential fusion partners due to intergenic ALK rearrangements have also been discovered [ [3] Ou S.-H.I. Zhu V.W. Nagasaka M. Catalog of 5’ fusion partners in ALK-positive NSCLC circa 2020. JTO Clin. Res. Rep. 2020; 1100015 Abstract Full Text Full Text PDF Google Scholar ]. Even multiple breakpoint variants, such as EML4-ALK with at least 21 breakpoint variants in NSCLC, were detected in same fusion protein [ [4] Su Y. Long X. Song Y. Chen P. Li S. Yang H. et al. Distribution of ALK fusion variants and correlation with clinical outcomes in Chinese patients with non-small cell lung cancer treated with crizotinib. Target. Oncol. 2019; 14: 159-168 Crossref PubMed Scopus (21) Google Scholar ].