title: Prognostic value of mutational characteristics in gastrointestinal stromal tumors: a single-center experience in 275 cases.
abstract: The objective of this study was to investigate the impact of KIT/PDGFRA mutations on the prognosis of gastrointestinal stromal tumors (GISTs). In the present study, genotype analyses were performed based on GIST samples from 275 patients. The relationship between mutation and clinicopathological characteristics were explored. All factors were evaluated for their impacts on relapse-free survival (RFS). Briefly, the results of genotype analyses showed that mutations were identified in 258 (93.8 %) patients, and deletion was the most frequent type of mutation accounting for 47.3 % (122/258) of all mutation cases, followed by substitution (87/258, 33.7 %) and duplication (49/258, 19.0 %). Moreover, for KIT exon 11 mutation, the most frequently involved area was from codon 557 to 560. Deep analyses showed that the mutation types were correlated with tumor location (P = 0.005), tumor size (P = 0.022), mitosis rate (P < 0.001), risk grade (P < 0.001), and relapse (P = 0.004). Furthermore, delW557-K558 correlated with mitosis rate (P = 0.042) and relapse (P = 0.036), and delTyr568/570 correlated with tumor origin (P = 0.018). Most importantly, mitotic rate [HR = 2.901 (95 % CI 1.094-7.695), P = 0.032] and risk grade [HR = 9.629 (95 % CI 1.997-46.416), P = 0.005] would be the representative traditional prognostic factors, and deletion with >3 codons would be an novel independent predictor of poor outcome for RFS in GIST patients with deletion mutation of KIT exon 11 [HR = 7.970 (95 % CI 1.774-35.803), P = 0.007]. All results indicated that mutation determined clinicopathological features and prognosis of GISTs, and more than three codons involvement may be a novel adverse indicator.
authors: Department of General Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, P.O. Box 200127, Shanghai, China.
authors: Ming
authors: M
authors: Wang
authors: Jia
authors: J
authors: Xu
authors: Wenyi
authors: W
authors: Zhao
authors: Lin
authors: L
authors: Tu
authors: Weiqing
authors: W
authors: Qiu
authors: Chaojie
authors: C
authors: Wang
authors: Yangyin
authors: Y
authors: Shen
authors: Qiang
authors: Q
authors: Liu
authors: Hui
authors: H
authors: Cao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003062:Codon; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D011379:Prognosis; D012008:Recurrence; D012306:Risk; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics*
chemical_list: D003062:Codon