Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
Molecular Diagnostics, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India.
J Clin Pathol. 2022 Mar;75(3):164-167. doi: 10.1136/jclinpath-2020-207212. Epub 2020 Dec 28.
The emergence of sophisticated next generation sequencing (NGS) based technologies in routine molecular diagnostics has paved the way for robust and accurate detection of variants which may otherwise be missed on single gene testing. This study aims at highlighting the same premise in EGFR mutated non-small cell lung carcinoma (NSCLC).
1350 cases of NSCLC were screened, of which 490 EGFR mutated cases were taken. The clinical records and molecular features were evaluated retrospectively to determine those cases which were missed on single gene testing.
Among these 490 cases, there were 11 (2.2%) cases which tested negative on single gene testing using polymerase chain reaction (therascreen). These were then subjected to NGS based testing and were positive for 13 different mutations. Five out of the 11 cases received tyrosine kinase inhibitor (TKI) based on the NGS test outcome. Four cases with exon 20 insertion mutations were not offered TKI as these mutations are known to be intrinsically resistant to TKI therapy. The five patients who have been treated with TKI have shown fair response and have not progressed to date.
We demonstrated a potentially preferable way to profile treatment-naïve patients with NSCLC by NGS and from our early experience in mutant cases, the advantages of NGS over single gene testing is clearly evident.
先进的下一代测序（NGS）技术在常规分子诊断中的出现，为稳健而准确地检测可能在单基因检测中遗漏的变异铺平了道路。本研究旨在强调这一前提在 EGFR 突变型非小细胞肺癌（NSCLC）中的作用。
筛选了 1350 例 NSCLC 病例，其中 490 例为 EGFR 突变病例。回顾性评估临床记录和分子特征，以确定在单基因检测中遗漏的病例。
在这 490 例中，有 11 例（2.2%）在使用聚合酶链反应（therascreen）的单基因检测中呈阴性。然后对这些病例进行基于 NGS 的检测，结果显示存在 13 种不同的突变。其中 5 例根据 NGS 检测结果接受了酪氨酸激酶抑制剂（TKI）治疗。4 例存在外显子 20 插入突变的患者未接受 TKI 治疗，因为这些突变已知对 TKI 治疗具有内在耐药性。接受 TKI 治疗的 5 名患者表现出良好的反应，迄今为止尚未进展。
我们通过 NGS 为治疗初治 NSCLC 患者提供了一种潜在的优选方法，根据我们在 突变病例中的早期经验，NGS 相对于单基因检测的优势显而易见。
