胸腺瘤基因学突变特点

发布时间：2019-02-13 06:58

【摘要】：背景:胸腺瘤是一种由胸腺上皮分化而来,多发于前纵膈的肿瘤。由于此种疾病的低发生率阻碍了大量临床试验及研究的开展。目前胸腺瘤领域的进展缓慢,治疗手段主要依靠手术切除及术后放化疗。随着二代测序(NGS)技术不断发展,NGS已能够检测肿瘤全基因组或特定序列的基因突变情况。为了适应个体化精准的靶向治疗趋势,本研究中我们将采用二代测序技术分析各型胸腺瘤中所具有的分子学特点。旨在通过这种高效且精准的方法分析胸腺瘤疾病发生及进展的分子学机制,为胸腺瘤的诊断及治疗方法提供指导。方法:在本项研究中24例研究对象均来自与2011-2015年在我们科行手术治疗并且病理确诊为胸腺瘤。临床分期使用Masaoka分级。入组前已获得患者书面同意。二代测序技术选用燃石朗康TM V2.0[LK103]检测项目,通过康系panel.56对配对的正常组织与肿瘤组织共56个肿瘤相关基因进行检测分析,将分析结果与样本的WHO病理分型、Masaoka临床分期、患者无进展生存期(Progression Free Survival,PFS)及总生存期(Overall survival,OS)进行比较分析。4.本研究中,CDKN2A突变仅出现于胸腺癌患者中,突变频率12%。结果:1.送检24例样本中,9例患者未检测到基因突变。胸腺瘤患者突变率为50%(N=6),胸腺癌患者突变率为75%(N=9)。2.胸腺癌中突变率最高的基因为TP53(N=3),胸腺瘤中突变率最高的基因为BRCA1(N=3)。3.CDKN2A在胸腺癌中突变频率仅次于TP53,并且该突变基因仅存在胸腺癌样本中。结论:1.胸腺瘤及胸腺癌的分子学特征复杂多变,基因突变种类繁多但重复突变基因少,络氨酸激酶受体基因突变罕见。2.恶性程度较高的胸腺癌及B3型胸腺瘤具有较高的突变频率。3.TP53突变与胸腺瘤的恶性程度相关,存在TP53或CDKN2A突变的胸腺瘤患者可能存在较短的生存期。
[Abstract]:Background: thymoma is a kind of tumor derived from thymic epithelium and mainly located in the anterior mediastinum. The low incidence of the disease hinders the development of a large number of clinical trials and studies. At present, the progress of thymoma is slow, the treatment mainly depends on surgical resection and postoperative radiotherapy and chemotherapy. With the development of second-generation sequencing (NGS), NGS has been able to detect gene mutations in the whole genome or specific sequence of tumor. In order to adapt to the trend of individualized targeted therapy, we will analyze the molecular characteristics of thymoma by second generation sequencing technique. The purpose of this paper is to analyze the molecular mechanism of the occurrence and progression of thymoma by this efficient and accurate method, and to provide guidance for the diagnosis and treatment of thymoma. Methods: Twenty-four cases of thymoma were treated in our department from 2011 to 2015 and pathologically diagnosed as thymoma. Masaoka grading was used in clinical staging. The patient's written consent has been obtained prior to admission. The second generation sequencing technique selected TM V2.0 [LK103] to detect and analyze 56 tumor-related genes in matched normal tissues and tumor tissues by Kang line panel.56. The results were compared with the WHO pathological typing of the samples. Masaoka staging, progressive survival time (Progression Free Survival,PFS) and total survival time (Overall survival,OS) were compared and analyzed. 4. 4. In this study, CDKN2A mutations were found only in patients with thymic cancer, with a mutation frequency of 12. Results: 1. No mutation was detected in 9 of 24 samples. The mutation rate was 50% in thymoma patients and 75% in thymic carcinoma patients. 2. 2. The highest mutation rate in thymic carcinoma was TP53 (N3), and the highest mutation rate in thymoma was BRCA1 (N3). The mutation frequency of 3.CDKN2A was second only to TP53, in thymocarcinoma and only existed in thymocarcinoma samples. Conclusion: 1. The molecular characteristics of thymoma and thymic carcinoma are complex and changeable. There are many kinds of gene mutations, but few repeat mutations, and the mutation of complex aminokinase receptor gene is rare. 2. The higher malignant degree of thymoma and type B3 thymoma have higher mutation frequency. 3.TP53 mutation is associated with the malignant degree of thymoma, and the patients with TP53 or CDKN2A mutation may have a shorter survival period.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R736.3

【相似文献】