Guo Jintao, Ge Qichao, Yang Fan, Wang Sheng, Ge Nan, Liu Xiang, Shi Jing, Fusaroli Pietro, Liu Yang, Sun Siyu
Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Innovative Research Center for Integrated Cancer Omics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Cancers (Basel). 2022 Dec 6;14(23):6008. doi: 10.3390/cancers14236008.
Small gastrointestinal stromal tumors (GISTs) are defined as tumors less than 2 cm in diameter, which are often found incidentally during gastroscopy. There is controversy regarding the management of small GISTs, and a certain percentage of small GISTs become malignant during follow-up. Previous studies which used Sanger targeted sequencing have shown that the mutation rate of small GISTs is significantly lower than that of large tumors. The aim of this study was to investigate the overall mutational profile of small GISTs, including those of wild-type tumors, using whole-exome sequencing (WES) and Sanger sequencing.
Thirty-six paired small GIST specimens, which were resected by endoscopy, were analyzed by WES. Somatic mutations identified by WES were confirmed by Sanger sequencing. Sanger sequencing was performed in an additional 38 small gastric stromal tumor samples for examining hotspot mutations in KIT, PDGFRA, and BRAF.
Somatic C-KIT/PDGFRA mutations accounted for 81% of the mutations, including three novel mutation sites in at exon 11, across the entire small gastric stromal tumor cohort ( = 74). In addition, 15% of small GISTs harbored previously undescribed BRAF-V600E hotspot mutations. No significant correlation was observed among the genotype, pathological features, and clinical classification.
Our data revealed a high overall mutation rate (~96%) in small GISTs, indicating that genetic alterations are common events in early GIST generation. We also identified a high frequency of oncogenic BRAF-V600E mutations (15%) in small GISTs, which has not been previously reported.
小胃肠道间质瘤（GIST）定义为直径小于2 cm 的肿瘤，常在胃镜检查时偶然发现。小GIST的治疗存在争议，且一定比例的小GIST在随访过程中会发生恶变。以往使用桑格靶向测序的研究表明，小GIST的突变率显著低于大肿瘤。本研究旨在利用全外显子测序（WES）和桑格测序研究小GIST的整体突变谱，包括野生型肿瘤的突变谱。
对36例经内镜切除的配对小GIST标本进行WES分析。通过桑格测序确认WES鉴定出的体细胞突变。另外对38例小胃间质瘤样本进行桑格测序，以检测KIT、PDGFRA和BRAF的热点突变。
在整个小胃间质瘤队列（n = 74）中，体细胞C-KIT/PDGFRA突变占突变的81%，包括外显子11的3个新突变位点。此外，15%的小GIST存在先前未描述的BRAF-V600E热点突变。未观察到基因型、病理特征和临床分类之间存在显著相关性。
我们的数据显示小GIST的总体突变率较高（约96%），表明基因改变是早期GIST发生过程中的常见事件。我们还在小GIST中发现了高频的致癌BRAF-V600E突变（15%），这在以前尚未见报道。
