A mutation analysis of the EGFR pathway genes, RAS, EGFR, PIK3CA, AKT1 and BRAF, and TP53 gene in thymic carcinoma and thymoma type A/B3
A mutation analysis of the EGFR pathway genes, RAS, EGFR, PIK3CA, AKT1 and BRAF, and TP53 gene in thymic carcinoma and thymoma type A/B3
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DOI：
10.1111/his.13936
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发表时间：
2019-10-03
期刊：
影响因子：
6.4
通讯作者：
Inagaki, Hiroshi
中科院分区：
文献类型：
--
作者：
Sakane, Tadashi;Murase, Takayuki;Inagaki, Hiroshi
胸腺癌是一种罕见的疾病，通常有致命的后果。在胸腺癌中表皮生长因子受体（EGFR）信号通路和TP53的基因突变还没有得到很好的分析。方法和结果我们检查了一个大型胸腺癌和A/B3型胸腺瘤队列，并寻找RAS家族、EGFR、PIK 3CA、AKT 1、BRAF和TP 53的基因突变。在54例胸腺癌中，10例检测到RAS家族突变，2例检测到EGFR突变，1例检测到PIK3CA突变，1例检测到AKT1突变，5例检测到TP53突变，BRAF突变未检测到。33例A/B3型胸腺瘤中，1例HRAS基因突变，2例PIK3CA基因突变，1例AKT1基因突变。所有这些突变都是错义型激活突变。RAS家族突变在胸腺癌中的发生率显著高于A/B3型胸腺瘤（P = 0.0461）。一项针对胸腺鳞状细胞癌病例（n = 44）的预后分析显示，在单变量分析中，EGFR通路突变患者（n = 9）的总生存期显著短于无突变患者（P = 0.0173）。随后，在多变量分析中，EGFR通路突变被选为总生存率差的独立因素（P = 0.0389）。结论EGFR通路和TP53基因突变在胸腺癌中可能存在，EGFR通路突变可能与胸腺鳞癌患者预后不良有关。胸腺癌基因突变的治疗意义有待进一步阐明。
Aims Thymic carcinoma is rare and usually has a fatal outcome. Gene mutations in the epidermal growth factor receptor (EGFR) signalling pathway and TP53 have not been well analysed in thymic carcinoma. Methods and results We examined a large cohort of thymic carcinoma and thymoma type A/B3 and looked for gene mutations in the RAS family, EGFR, PIK3CA, AKT1, BRAF and TP53. Among 54 thymic carcinoma cases, RAS family mutations were detected in 10 cases, EGFR in two, PIK3CA in one, AKT1 in one, BRAF in none and TP53 in five. Among 33 thymoma type A/B3 cases, HRAS gene mutation were found in one, PIK3CA in two and AKT1 in one. All these mutations were those of missense type activating mutations. RAS family mutations were significantly more frequent in thymic carcinoma than in thymoma type A/B3 (P = 0.0461). A prognostic analysis focusing on thymic squamous cell carcinoma cases (n = 44) showed that the overall survival was significantly shorter in patients with EGFR pathway mutations (n = 9) than in those without in a univariate analysis (P = 0.0173). Subsequently, EGFR pathway mutations were selected as an independent factor for a poor overall survival in a multivariate analysis (P = 0.0389). Conclusions Mutations in the EGFR pathway and TP53 in thymic carcinoma may be frequent, and the EGFR pathway mutations may be associated with a poor prognosis in thymic squamous cell carcinoma patients. The therapeutic significance of gene mutations in thymic carcinoma should be further clarified.