Vikberg Ann-Louise, Vooder Tõnu, Lokk Kaie, Annilo Tarmo, Golovleva Irina
Department of Medical Biosciences/Medical and Clinical Genetics, Umeå University, Umeå, Sweden.
Department of Thoraic Surgery, Helios Klinikum Krefeld, Krefeld, Germany.
Onco Targets Ther. 2017 Oct 11;10:4969-4979. doi: 10.2147/OTT.S138420. eCollection 2017.
KIF23 was recently suggested to be a potential molecular target for the treatment of lung cancer. This proposal is based on elevated expression of in several tumors affecting breast, lung, brain, and liver, and also on the presence of mutations in melanoma and colorectal cancer. Recently, we identified a mutation in the gene causing a rare hereditary form of dyserythropoietic anemia (CDA III) with predisposition to blood cancer. We suggested that overexpression in tumors might be due to the presence of activating somatic mutations, and therefore, mutation screening of the in 15 non-small-cell lung cancer (NSCLC) cases with elevated expression level of was undertaken. Eight sequence variants were found in all samples. Furthermore, one variant was present in two cases, and one variant was case specific. Nine variants were previously reported while one variant lacks frequency information. Nine of ten cases available for single nucleotide polymorphism-array analysis demonstrated aberrant karyotypes with additional copy of entire chromosome 15. Thus, no activating somatic mutations in coding regions of the were found. Furthermore, no mutations were detected in cell cycle genes homology region in promoter responsible for p53-dependent repression of expression. We showed that the elevated level of could be due to additional copy of chromosome 15 demonstrated in 90% of NSCLC cases analyzed in this study. Considering the crucial role of in the final step of mitosis, the gene is a potential molecular marker, and for better understanding of its role in cancer development, more tumors should be analyzed.
KIF23最近被认为是治疗肺癌的一个潜在分子靶点。这一观点基于其在影响乳腺、肺、脑和肝脏的几种肿瘤中表达升高，以及在黑色素瘤和结直肠癌中存在该基因突变。最近，我们在一个导致罕见遗传性异常红细胞生成性贫血（CDA III型）并易患血癌的基因中发现了一个突变。我们认为肿瘤中该基因的过表达可能是由于存在激活的体细胞突变，因此，我们对15例KIF23表达水平升高的非小细胞肺癌（NSCLC）病例进行了该基因突变筛查。在所有样本中发现了8个序列变异。此外，有两个病例存在一个变异，还有一个变异是病例特异性的。9个变异先前已有报道，而有一个变异缺乏频率信息。在可用于单核苷酸多态性阵列分析的10个病例中，有9例显示出异常核型，伴有整条15号染色体的额外拷贝。因此，在KIF23编码区未发现激活的体细胞突变。此外，在负责p53依赖的KIF23表达抑制的启动子的细胞周期基因同源区域未检测到突变。我们发现，本研究分析的90%的NSCLC病例中KIF23水平升高可能是由于15号染色体的额外拷贝。考虑到KIF23在有丝分裂最后阶段的关键作用，该基因是一个潜在的分子标志物，为了更好地理解其在癌症发生中的作用，应该分析更多的肿瘤。
