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Molecular profile in Paraguayan colorectal cancer patients, towards to a precision medicine strategy

机译:巴拉圭大肠癌患者的分子概况,以寻求精确的医学策略

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Somatic mutation analysis and evaluation of microsatellite instability (MSI) have become mandatory for selecting personalized therapy strategies for advanced colorectal cancer and are not available as routine methods in Paraguay. The aims of this study were to analyze the molecular profile as well as the microsatellite status in a series of advanced colorectal patients from two public hospitals from Paraguay, to introduce these methodologies in the routine practice to guide the therapeutic decisions. Thirty‐six patients diagnosed with advanced colorectal cancer from two referent public hospitals from Paraguay were recruited from May 2017 to February 2018. Sequenom Mass spectrometry, Oncocarta Panel V.1 was applied to analyze the mutational profile from formalin‐fixed paraffin‐embedded samples. The microsatellite status was tested by immunohistochemistry (IHC). The mean age of the patients was 52?years with a range from 20 to 74?years. Eighty‐three percent of the patients included in the study have advanced‐stage tumors at the moment of the diagnosis. Sixteen patients (44.4%) were wild‐type for all the oncogene regions analyzed with the Oncocarta panel. Thirty‐two hot‐spot pathogenic variants on seven oncogenes, among 20 patients (55.6%), were identified, including KRAS, NRAS, BRAF, PI3KCA, FGFR, epidermal growth factor receptor, and PDGFRA. Moreover, 14 (38.8%) of these patients presented pathogenic variants in KRAS/NRAS or BRAF genes that have implications in the clinical practice decisions. Five patients (14%) presented MSI. The IHC study for microsatellite status and the molecular profile analysis through Sequenom mass spectrometry are feasible and useful methods, due to identify those patient candidates for targeted therapies and for the budgetary calculations of the National Health Plans.
机译:体细胞突变分析和微卫星不稳定性(MSI)评估已成为选择晚期大肠癌个性化治疗策略的强制性方法,在巴拉圭尚无常规方法。这项研究的目的是分析来自巴拉圭两家公立医院的一系列晚期大肠癌患者的分子谱以及微卫星状态,以将这些方法学引入常规实践中以指导治疗决策。从2017年5月至2018年2月,从巴拉圭两家公立公立医院招募了36例被诊断为晚期大肠癌的患者。应用Sequenom质谱分析,Oncocarta Panel V.1分析福尔马林固定石蜡包埋的样本的突变情况。通过免疫组织化学(IHC)测试微卫星状态。患者的平均年龄为52岁,范围为20至74岁。在诊断中,研究中包括的患者中有83%患有晚期肿瘤。在癌基因组分析的所有癌基因区域中,有16例(44.4%)为野生型。在20例患者中(55.6%),在7个癌基因上发现了32个热点病原体,包括KRAS,NRAS,BRAF,PI3KCA,FGFR,表皮生长因子受体和PDGFRA。此外,这些患者中有14位(38.8%)表现出KRAS / NRAS或BRAF基因的致病变异,这些变异对临床实践决策具有影响。五名患者(14%)出现了MSI。 IHC有关微卫星状态的研究以及通过Sequenom质谱仪进行分子谱分析的方法是可行和有用的方法,这是因为确定了那些可用于靶向治疗的患者以及国家卫生计划的预算计算方法。

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