Anaplastic lymphoma kinase gene rearrangement in non-small-cell lung cancer in a Brazilian population

Abstract

Lung cancer is the leading cause of cancer deaths worldwide (1). Non-small-cell lung carcinoma (NSCLC), which represents approximately 80% of all lung cancer cases, is frequently diagnosed at advanced stages of the disease and is associated with short survival time. Although the prognosis of this disease remains poor, significant advances in the genetics and treatment of NSCLC have been made in recent years. In 2007, Soda et al. (2) identified the transforming EML4-ALK fusion gene in 6.7% of NSCLC patients. This fusion transcript, which presents potent oncogenic activity both in vitro and in vivo (2,3), is formed by the translocation of the echinoderm microtubule-associated protein-like 4 (EML4) gene (2p21) and anaplastic lymphoma kinase (ALK) gene (2p23). Subsequent studies have shown that between two and eight percent of all NSCLC cases may harbor ALK rearrangements, which are almost always mutually exclusive with EGFR and KRAS mutations. Moreover, these patients are frequently younger, non- or light smokers and have adenocarcinomas (2),. Recently, crizotinib, an orally available small-molecule inhibitor of the ALK tyrosine kinase, was approved for the treatment of ALK-rearranged NSCLC patients, with successful results (24-29). The two most widely used methods for the diagnosis of ALK-rearranged NSCLC are fluorescence in situ hybridization (FISH) and immunohistochemistry. Because there is no information about the prevalence and clinical characteristics of ALK-rearranged NSCLC in Latin America in the literature, the aim of this study was to evaluate NSCLC with ALK rearrangement in Brazilian patients.