Mavroeidis Leonidas, Metaxa-Mariatou Vassiliki, Papoudou-Bai Alexandra, Lampraki Angeliki Maria, Kostadima Lida, Tsinokou Ilias, Zarkavelis George, Papadaki Alexandra, Petrakis Dimitrios, Gκoura Stefania, Kampletsas Eleftherios, Nasioulas George, Batistatou Anna, Pentheroudakis George
Department of Medical Oncology, School of Medicine, Ioannina, Greece.
Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece.
ESMO Open. 2018 Apr 6;3(3):e000335. doi: 10.1136/esmoopen-2018-000335. eCollection 2018.
Gastrointestinal stromal tumours (GIST) are mesenchymal neoplasms that usually carry an activating mutation in or platelet-derived growth factor receptor alpha () genes with predictive and prognostic significance. We investigated the extended mutational status of GIST in a patient population of north-western Greece in order to look at geopraphic/genotypic distinctive traits.
Clinicopathological and molecular data of 38 patients diagnosed from 1996 to 2016 with GIST in the region of Epirus in Greece were retrospectively assessed. Formalin-fixed paraffin-embedded tumours were successfully analysed for mutations in 54 genes with oncogenic potential. Next generation sequencing was conducted by using the Ion AmpliSeqCancer Hotspot Panel V.2 for DNA analysis (Thermofisher Scientific).
Among 38 tumours, 24 (63.16%) and seven (18.42%) of the tumours harboured mutations in the and genes, respectively, while seven (18.42%) tumours were negative for either or mutation. No mutations were detected in five (13.16%) cases. Concomitant mutations of and fibroblast growth factor receptor 3 () genes were observed in two patients with gene mutation. Two patients with / wild-type GIST had mutations in either or phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha () genes. There was no significant survival difference regarding the exonic site of mutation in either or gene. The presence of a mutation in pathway effectors downstream of or , such as , or , was associated with poor prognosis. Adverse prognosticators were also high mitotic index and the advanced disease status at diagnosis.
We report comparable incidence of and mutation in patients with GIST from north-western Greece as compared with cohorts from other regions. Interestingly, we identified rare mutations on , and genes in patients with poor prognosis.
胃肠道间质瘤（GIST）是一种间叶组织肿瘤，通常在KIT或血小板衍生生长因子受体α（PDGFRA）基因中携带具有预测和预后意义的激活突变。我们调查了希腊西北部患者群体中GIST的扩展突变状态，以观察地理/基因型特征。
回顾性评估了1996年至2016年在希腊伊庇鲁斯地区诊断为GIST的38例患者的临床病理和分子数据。对福尔马林固定石蜡包埋的肿瘤成功分析了54个具有致癌潜力的基因中的突变。使用Ion AmpliSeqCancer Hotspot Panel V.2进行下一代测序以进行DNA分析（赛默飞世尔科技公司）。
在38个肿瘤中，分别有24个（63.16%）和7个（18.42%）肿瘤在KIT和PDGFRA基因中存在突变，而7个（18.42%）肿瘤KIT或PDGFRA突变均为阴性。5例（13.16%）病例未检测到突变。在2例KIT基因突变患者中观察到KIT和成纤维细胞生长因子受体3（FGFR3）基因的伴随突变。2例KIT/PDGFRA野生型GIST患者在PIK3CA或磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α（PIK3CA）基因中存在突变。KIT或PDGFRA基因外显子位点的突变在生存方面无显著差异。KIT或PDGFRA下游通路效应器（如NRAS、BRAF或PIK3CA）中存在突变与预后不良相关。不良预后因素还包括高有丝分裂指数和诊断时的晚期疾病状态。
我们报告希腊西北部GIST患者中KIT和PDGFRA突变的发生率与其他地区队列相当。有趣的是，我们在预后不良的患者中鉴定出了NRAS、BRAF和PIK3CA基因的罕见突变。
