Rare gene mutations of wild-type gastrointestinal stromal tumors

Abstract

Abstract Background Wild-type (WT) gastrointestinal stromal tumors (GISTs) are a subgroup of GISTs lacking KIT and PDGFRA mutations. Further gene and clinical characterization of WT GISTs will help determining patient prognosis and developing targeted therapy. Methods A total of 105 patients with GISTs were enrolled, and 15 were WT GISTs. Immunohistochemistry (IHC) staining, Sanger sequencing (SS) and next generation sequencing (NGS) approach were used to analyze WT GISTs. Results The 15 WT GISTs (median age, 50 [range, 9–82] years; 66.6% female; 73.3% stomach) showed the following gene mutations. SDH-deficient WT GISTs (n = 7) had mutations in SDHA, CCND1, RB1, FLT3, TP53 and SDHD. Patient with SDHA (c.G1690A), CCND1, RB1, and FLT3 (c.C2917T) mutations was a middle-aged women, stomach tumor location and high proliferative activity. Patients with TP53 ( c.300_308delGAAAACCTA; c.G841T) mutation or coexisting mutation of SDHD (c.336de1T) were showed high p53 expression, middle-aged women, stomach tumor location. Non-SDH-deficient WT GISTs (n = 8) had mutations in BRAF, TERT, and CDH1. Two patients harbored BRAF (V600E) mutation: one was a micro-GISTs, elderly female, stomach location, and low risk, the other was accompany TERT mutation, elderly male, small intestine location, and high risk. Patient with CDH1 (c.G2356A) mutation was a middle-aged male, duodenum tumor location and high risk. Conclusions We identified rare gene mutations of CCND1, RB1, FLT3, TERT, and CDH1 in WT GISTs. what's more, mutations of CCND1, RB1, TP53, BRAF, and CDH1 were likely to show high risk and malignant behavior which will provided new insights into the biology and mutations in WT GISTs.