Unproductive Effects of ALK Gene Amplification and Copy Number Gain in Non-Small-Cell Lung Cancer. ALK Gene Amplification and Copy Gain in NSCLC

摘要

The Anaplastic Lymphoma Kinase (ALK) gene is known to be affected by several genetic alterations, such as rearrangement, amplification and point mutation. The main goal of this study was to comprehensively analyze amplification ( -A) and gene copy number gain ( ) in a large cohort of non-small-cell lung cancer (NSCLC) patients in order to evaluate the effects on mRNA and protein expression. locus number status was evaluated in 578 NSCLC cases by fluorescence in situ hybridization (FISH). In addition, ALK immunohistochemistry and ALK mRNA in situ hybridization were performed. Out of 578 cases, 17 cases showed -A. In addition, 14 cases presented K-CNG and 72 cases presented chromosome 2 polyploidy. None of those carrying -A and -CNG showed either ALK immunohistochemical expression or ALK mRNA expression through in situ hybridization. We observed a high frequency of extra copies of the gene. : Our findings demonstrated that -A is not involved in mRNA production and consequently is not involved in protein production; these findings support the hypothesis that -A might not play a role in the pathogenesis of NSCLC, underlining the absence of a specific clinical application.