Das Kakoli, Tay Mandy Li Ian, Yong Elena Yaqing, Chuah Khoon Leong
Department of Pathology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore.
Sci Rep. 2025 Jul 1;15(1):20740. doi: 10.1038/s41598-025-08039-6.
Targeted next generation sequencing (NGS) using multigene panels has become an effective tool for comprehensive genomic analysis in cancer, overcoming limitations of single gene assays. Nonetheless, outsourcing these assays to external laboratories and the extended turnaround time (~ 3 weeks) required for obtaining results may impede timely clinical management of cancer patients. We developed an oncopanel targeting 61 cancer-associated genes and validated its efficacy by performing NGS on 43 unique samples including clinical tissues, external quality assessment samples, and reference controls. The assay detected 794 mutations including all 92 known variants from orthogonal methods. Overall performance measures of the assay showed 99.99% repeatability and 99.98% reproducibility. Likewise, sensitivity to detect unique variants was 98.23%, with specificity at 99.99%, precision at 97.14% and accuracy at 99.99% all at 95% CI. Notably, clinically actionable mutations were observed in key genes such as KRAS, EGFR, ERBB2, PIK3CA, TP53 and BRCA1. The average turnaround time from sample processing to results was reduced to 4 days. These findings demonstrate a sensitive, high throughput oncopanel that is suitable for use in routine clinical testing. The shorter turnaround time of the assay has the potential to significantly improve patient care by facilitating more timely and personalized clinical interventions.
使用多基因检测板的靶向新一代测序（NGS）已成为癌症综合基因组分析的有效工具，克服了单基因检测的局限性。尽管如此，将这些检测外包给外部实验室以及获得结果所需的较长周转时间（约3周）可能会妨碍癌症患者的及时临床管理。我们开发了一种针对61个癌症相关基因的肿瘤检测板，并通过对43个独特样本（包括临床组织、外部质量评估样本和参考对照）进行NGS来验证其有效性。该检测方法检测到794个突变，包括来自正交方法的所有92个已知变体。该检测方法的总体性能指标显示重复性为99.99%，再现性为99.98%。同样，检测独特变体的灵敏度为98.23%，特异性为99.99%，精确度为97.14%，准确度为99.99%（均在95%置信区间）。值得注意的是，在KRAS、EGFR、ERBB2、PIK3CA、TP53和BRCA1等关键基因中观察到了具有临床可操作性的突变。从样本处理到结果的平均周转时间缩短至4天。这些发现证明了一种灵敏、高通量的肿瘤检测板，适用于常规临床检测。该检测方法较短的周转时间有可能通过促进更及时和个性化的临床干预来显著改善患者护理。
