文章：

《KIT/PDGFRA突变型与野生型胃肠道间质瘤（GIST）的分子谱特征及其临床病理相关性分析：科威特某三级医疗中心18年诊疗经验总结》

Molecular Profiling ofKIT/PDGFRA-Mutant and Wild-Type Gastrointestinal Stromal Tumors (GISTs) with Clinicopathological Correlation: An 18-Year Experience at a Tertiary Center in Kuwait

原文发布日期：21 August 2024

DOI: 10.3390/cancers16162907

类型: Article

开放获取: 是

英文摘要：

In gastrointestinal stromal tumors (GISTs), identifying prototypical mutations in theKIT/PDGFRAoncogenes, or in rare alternate genes, is essential for prognostication and predicting response to tyrosine kinase inhibitors. Conversely, wild-type GISTs (WT-GIST), which lack known mutations, have limited treatment options. Data on the mutational landscape of GISTs and their impact on disease progression are very limited in Kuwait. Using a targeted next-generation sequencing panel, we investigated the spectrum and frequency ofKIT,PDGFRA, and RAS-pathway-related mutations in 95 out of 200 GISTs diagnosed at Kuwait Cancer Center from 2005 to 2023 and assessed their correlation with clinicopathological parameters. Among the 200 tumors (median age 55 years; 15–91), 54% originated in the stomach, 33% in the small bowel, 7% in the colorectum, 1.5% in the peritoneum, and 4.5% had an unknown primary site. Of the 95 molecularly profiled cases, 88% had a mutation:KIT(61%),PDGFRA(25%),NF1(2%), and oneNTRK1rearrangement. Ten WT-GISTs were identified (stomach = 6, small bowel = 2, and colorectum = 2). WT-GISTs tended to be smaller (median 4.0 cm; 0.5–8.0) (p= 0.018), with mitosis ≤5/5 mm2, and were of lower risk (p= 0.019).KITmutations were an adverse indicator of disease progression (p= 0.049), while wild-type status did not significantly impact progression (p= 0.934). The genetic landscape in this cohort mirrors that of global studies, but regional collaborations are needed to correlate outcomes with genetic variants.

摘要翻译： 

在胃肠道间质瘤（GIST）中，识别KIT/PDGFRA癌基因或罕见替代基因中的典型突变对于预后判断和预测酪氨酸激酶抑制剂疗效至关重要。相反，缺乏已知突变的野生型GIST（WT-GIST）治疗选择有限。科威特地区关于GIST突变谱及其对疾病进展影响的数据非常匮乏。本研究采用靶向二代测序技术，对2005年至2023年科威特癌症中心诊断的200例GIST中的95例进行了KIT、PDGFRA及RAS通路相关突变的频谱与频率分析，并评估其与临床病理参数的相关性。200例肿瘤患者（中位年龄55岁；范围15-91岁）中，54%原发于胃，33%原发于小肠，7%原发于结直肠，1.5%原发于腹膜，4.5%原发部位不明。在完成分子谱分析的95例中，88%检测到突变：KIT（61%）、PDGFRA（25%）、NF1（2%）及1例NTRK1重排。共发现10例WT-GIST（胃6例、小肠2例、结直肠2例）。WT-GIST通常体积较小（中位直径4.0 cm；范围0.5-8.0）（p=0.018），核分裂象≤5/5 mm²，且风险等级较低（p=0.019）。KIT突变是疾病进展的不良预测指标（p=0.049），而野生型状态对疾病进展无显著影响（p=0.934）。本队列的遗传学特征与全球研究结果一致，但需要开展区域合作以进一步明确遗传变异与临床结局的关联。

原文链接：

Molecular Profiling ofKIT/PDGFRA-Mutant and Wild-Type Gastrointestinal Stromal Tumors (GISTs) with Clinicopathological Correlation: An 18-Year Experience at a Tertiary Center in Kuwait