KIT/PDGFRA野生型胃肠间质瘤的分子与临床病理特征OA

Objective To investigate the molecular and clinicopathological characteristics and prognosis of wild-type gastrointestinal stromal tumors(wtGIST).Methods 13 cases initially identified as wtGIST by Sanger sequenc-ing were collected.Next-generation sequencing(NGS)was employed to detect 689 tumor-related genes.Among these,11 cases were confirmed as KIT/PDGFRA wtGIST by NGS,and their clinical pathological features,molecular characteristics,and follow-up data were systematically analyzed.Results Among the 13 Sanger-sequenced wtGIST cases,2 harbored p.N659Y and p.N659K mutations in PDGFRA exon 14 by NGS.Among the remaining 11 KIT/PDGFRA wtGIST cases,NGS identified 5 with NF1 gene mutations,1 carrying SDHA gene germline pathogenic muta-tion,and 5 with no definite driver gene mutations.Among the 11 KIT/PDGFRA wtGIST cases,there were 4 males and 7 females.Age ranged from 26 to 75 years,with a mean of 54.5 years.Tumor locations included the stomach(3 cases),duodenum(4 cases),and small intestine(4 cases).Histological subtypes were dominated by the spindle cell type(7 cases),followed by the epithelioid cell type(2 cases)and the mixed type(2 cases).Maximum tumor di-ameters ranged from 1.5 to 13.0 cm,with a mean of 6.4 cm.NIH risk classification showed 1 extremely low-risk case,3 low-risk cases,and 7 high-risk cases.Follow-up duration was from 9 to 93 months,with a mean of 35 months.The 5-year overall survival(OS)rate was 90.9%(1 death),and the 5-year disease-free survival(DFS)rate was 81.8%(2 recurrences,both in NF1 mutant cases).Conclusion Sanger sequencing for GIST should include PDGFRA exon 14 to accurately confirm KIT/PDGFRA wild-type status.NF1 inactivating mutations are important driver events in KIT/PDGFRA wtGIST,and their proportion may be higher than previously recognized.For wtGIST pa-tients,careful skin examination or neurofibromatosis-related features and detailed family history inquiry are essential to rule out neurofibromatosis.KIT/PDGFRA wtGIST exhibits substantial clinicopathological heterogeneity.Patients with NF1-mutant wtGIST featuring large tumor diameters,high mitotic counts,and high NIH risk may have an el-evated recurrence risk and should undergo enhanced imaging surveillance.