Department of Medical Genetics, Umraniye Education and Research Hospital, University of Health Sciences, Istanbul, Turkey.
Department of Histology and Embryology, Hamidiye International Faculty of Medicine, University of Health Sciences, Istanbul, Turkey.
Sci Rep. 2024 Nov 4;14(1):26581. doi: 10.1038/s41598-024-75208-4.
Lung cancer remains a significant health challenge, characterized by aberrant tissue growth within the pulmonary system. Early carcinogenic events often involve genomic instability and the emergence of a mutator phenotype. In this study, we aimed to explore the mutator phenotype in 89 patients diagnosed with non-small-cell lung cancer (NSCLC). RNA isolation from formalin-fixed paraffin-embedded (FFPE) tissue samples was performed using the Promega ReliaPrep RNA Miniprep System, facilitating gene amplification relevant to cancer through the Archer FusionPlexComprehensiveThyroid and Lung (CTL) kit. Next-generation sequencing (NGS) on the Illumina NextSeq platform enabled comprehensive analysis of target areas. Utilizing Archer Analysis software, secondary analyses involving data cleansing, alignment, and variant/fusion identification were executed against the human reference genome hg19 (GRCh37). Expression patterns were visualized using HeatMap graphics. Our findings revealed a notable presence of KRAS gene mutations in approximately 20% of NSCLC patients. Among these mutations, the G12C variant was predominant at 50%, followed by G12V and G12D variants at 11.2% each. Notably, patients harboring the G12C variant responded favorably to sotorasib medication. These results underscore the importance of mutational profiling and targeted therapeutic approaches in managing NSCLC, particularly highlighting the promising efficacy of sotorasib in G12C-mutated cases.
肺癌仍然是一个重大的健康挑战，其特征是肺部系统内的组织异常生长。早期致癌事件通常涉及基因组不稳定性和出现诱变表型。在这项研究中，我们旨在探索 89 名非小细胞肺癌 (NSCLC) 患者中的诱变表型。使用 Promega ReliaPrep RNA Miniprep 系统从福尔马林固定石蜡包埋 (FFPE) 组织样本中分离 RNA，通过 Archer FusionPlexComprehensiveThyroid 和 Lung (CTL) 试剂盒促进与癌症相关的基因扩增。Illumina NextSeq 平台上的下一代测序 (NGS) 实现了对目标区域的全面分析。利用 Archer Analysis 软件，针对人类参考基因组 hg19 (GRCh37) 执行了包括数据清理、比对和变体/融合识别在内的二级分析。使用 HeatMap 图形可视化表达模式。我们的研究结果显示，大约 20%的 NSCLC 患者存在 KRAS 基因突变。在这些突变中，G12C 变体占 50%，G12V 和 G12D 变体各占 11.2%。值得注意的是，携带 G12C 变体的患者对 sotorasib 药物治疗反应良好。这些结果强调了突变分析和靶向治疗方法在管理 NSCLC 中的重要性，特别是突出了 sotorasib 在 G12C 突变病例中的有前途的疗效。
