Department of Mental and Physical Health and Preventive Medicine, Pathology Unit, University of Campania "L. Vanvitelli", 80138 Naples, Italy.
Pathology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS "Fondazione Pascale", 80131 Naples, Italy.
Int J Mol Sci. 2020 Jul 12;21(14):4927. doi: 10.3390/ijms21144927.
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.
间变性淋巴瘤激酶(ALK)基因已知受到多种遗传改变的影响,如重排、扩增和点突变。本研究的主要目的是全面分析非小细胞肺癌(NSCLC)患者中大量队列的扩增(-A)和基因拷贝数增加(),以评估对 mRNA 和蛋白表达的影响。通过荧光原位杂交(FISH)评估了 578 例 NSCLC 病例中的 ALK 基因座数状态。此外,还进行了 ALK 免疫组化和 ALK mRNA 原位杂交。在 578 例病例中,有 17 例显示-A。此外,14 例存在 K-CNG,72 例存在染色体 2 三倍体。在携带-A 和-CNG 的病例中,均未通过原位杂交显示出 ALK 免疫组化表达或 ALK mRNA 表达。我们观察到基因的额外拷贝数频率很高。结论:我们的研究结果表明-A 不参与 mRNA 的产生,因此也不参与蛋白的产生;这些发现支持了-A 可能在 NSCLC 的发病机制中不起作用的假说,强调了缺乏特定的临床应用。