Faculty of Medicine, University of Ljubljana, SI‑1000 Ljubljana, Slovenia.
Department of Molecular Diagnostics, Institute of Oncology Ljubljana, SI‑1000 Ljubljana, Slovenia.
Oncol Rep. 2022 Sep;48(3). doi: 10.3892/or.2022.8382. Epub 2022 Jul 29.
In patients with gastrointestinal stromal tumors (GIST), it has become mandatory to determine the driver mutation in order to predict the response to standard treatment with tyrosine kinase inhibitors (TKI). A total of 10‑15% of all GIST lack activating mutations in KIT proto‑oncogene, receptor tyrosine kinase ()/platelet‑derived growth factor receptor alpha () and have been classified as wild‑type (WT) GIST. They are characterized by poor response to TKI. From a group of 119 metastatic GIST patients, 17 patients with WT GIST as determined by reverse transcription‑quantitative (RT‑q) PCR and Sanger sequencing were profiled by a targeted next‑generation sequencing (NGS) approach and their treatment outcome was assessed. In the present study, 41.2% of patients as WT GIST examined with RT‑qPCR and Sanger sequencing were confirmed to be carriers of pathogenic mutations by NGS and were responsive to TKI. The percentage of genuinely WT GIST in the present study thereby dropped from the initial 14.3% detected with the RT‑qPCR and Sanger sequencing to 7.6% after NGS. Their outcome was universally poor. The reliability of RT‑qPCR and direct Sanger sequencing results in this setting is therefore insufficient and it is recommended that NGS becomes a requirement for treatment decision at least in WT GIST as determined by RT‑qPCR and Sanger sequencing.
在胃肠道间质瘤（GIST）患者中，确定驱动突变已成为预测对酪氨酸激酶抑制剂（TKI）标准治疗反应的必要条件。所有 GIST 中约有 10-15%缺乏 KIT 原癌基因、受体酪氨酸激酶（）/血小板衍生生长因子受体α（）的激活突变，并被归类为野生型（WT）GIST。它们对 TKI 的反应较差。从 119 例转移性 GIST 患者中，通过逆转录定量（RT-q）PCR 和 Sanger 测序确定 17 例为 WT GIST 的患者通过靶向下一代测序（NGS）方法进行了分析，并评估了他们的治疗结果。在本研究中，通过 NGS 证实，用 RT-qPCR 和 Sanger 测序检查的 41.2%的 WT GIST 患者携带致病性突变，并对 TKI 有反应。因此，本研究中真正的 WT GIST 百分比从最初的 RT-qPCR 和 Sanger 测序检测到的 14.3%下降到 NGS 后的 7.6%。他们的预后普遍较差。因此，在这种情况下，RT-qPCR 和直接 Sanger 测序结果的可靠性不足，建议 NGS 成为至少在 RT-qPCR 和 Sanger 测序确定的 WT GIST 中进行治疗决策的必要条件。
