The huge number of detected somatic KIT mutations highlights the necessity of in silico analyses that are almost absent in the relevant medical literature. The aim of this study is to report the mutation spectrum analysis of exon 11 encoding the juxtamembrane (JM) domain of the KIT gene in a group of Syrian GIST patients. Forty-eight formalin-fixed paraffin-embedded GIST tissue samples, collected between 2006 and 2016, were retrieved from the pathological archives and analyzed for KIT exon 11 mutations by DNA sequencing. Structural/functional impact of detected variants was predicted using several bioinformatic tools. Twenty-one different variants have been detected in intron 10, exon 11, and intron 11 of the KIT gene, eight of which were novel changes. Mutations in exon 11 of the KIT gene were detected in 28 of 48 (58.3%) GIST patients and predicted to be pathogenic and cancer promoting. Specifically, age above 60 was very significantly associated with the negative selection of deletion mutations (p = .007), a phenomenon that points to deletion severity. Six bioinformatic tools have proved efficient in predicting the impact of detected KIT variations in view of published structural, experimental, and clinical findings.

中文翻译：

---

叙利亚 GIST 患者 KIT 近膜结构域突变的生物信息分析：拼图游戏完成

检测到的大量体细胞 KIT 突变凸显了计算机分析的必要性，而相关医学文献中几乎不存在这种分析。本研究的目的是报告一组叙利亚 GIST 患者中编码 KIT 基因近膜 (JM) 结构域的外显子 11 的突变谱分析。从病理档案中检索 2006 年至 2016 年间收集的 48 个福尔马林固定石蜡包埋的 GIST 组织样本，并通过 DNA 测序分析 KIT 外显子 11 突变。使用多种生物信息学工具预测检测到的变异的结构/功能影响。在 KIT 基因的内含子 10、外显子 11 和内含子 11 中检测到了 21 个不同的变异，其中 8 个是新的变化。在 48 名 GIST 患者中，有 28 名 (58.3%) 检测到 KIT 基因外显子 11 的突变，并预测该突变具有致病性和促癌性。具体来说，60 岁以上的年龄与缺失突变的阴性选择显着相关 (p = .007)，这种现象表明缺失的严重程度。鉴于已发表的结构、实验和临床发现，六种生物信息工具已被证明可以有效预测检测到的 KIT 变异的影响。