新一代测序技术在唾液腺恶性肿瘤中的相关研究

发布时间：2018-04-29 14:31

本文选题：透明细胞肉瘤 + 外显子组检测　；参考：《中国人民解放军医学院》2017年硕士论文

【摘要】：第一部分研究唾液腺透明细胞肉瘤存在NBN基因体细胞错义突变目的寻找唾液腺透明细胞肉瘤(CCS)基因组变异,筛选致癌基因,为CCS发病机制奠定基础。方法应用全外显子组测序分析CCS患者的肿瘤标本中可能存在的基因突变。利用Sanger测序验证患者外周血液及瘤旁组织中是否存在可疑基因突变。结果全外显子组测序以及Sanger测序验证结果显示在本例CCS中存在体细胞错义突变c.1061CT(p.P354L),其突变位点为NBN基因的第9个外显子。结论:本例CCS存在NBN上c.1061CT(p.P354L)体细胞错义突变。该突变的结果是脯氨酸转化为亮氨酸(p.P354L)导致NBN的有害突变。第二部分高通量测序研究黏液表皮样癌伴肺肌上皮癌转移的遗传机制目的寻找黏液表皮样癌伴肺性肌上皮癌转移的致癌基因,结合免疫组库为精准靶向治疗提供位点。方法选取患者肿瘤标本,①通过外显子测序找到癌变的致癌突变,并且进行-验证、注释和突变的功能预测。②通过全转录组测序找到差异表达的基因集,并进行基因功能预测和通路注释。③通过免疫组库找到患者异常的免疫细胞分子标记,并进行免疫组库与基因突变的关联分析。④通过多系统生物信息分析,深入研究该病的发病及转移机制,并结合免疫组库,寻找药物靶标。结果①外显子测序诊断结果,患者的Driver mutation gene (驱动突变基因)按照致癌的可能性从大到小排序分别为:WNT3, LNC, CCNE1, LC5A4等。②CCNE1基因的表达由癌旁的0.449353809上调到癌组织的1.411029095。该基因具有一个特异性靶向药物:ALISERTIB。结论CCNE1基因突变极可能是此病例的致癌原因,CCNE1基因有一个特异性靶向药物:ALISERTIB。
[Abstract]:The first part studies the existence of NBN gene somatic missense mutation in salivary gland clear cell sarcoma. Objective to search for the mutation of CCS genome in salivary gland clear cell sarcoma and to screen the oncogene to lay a foundation for the pathogenesis of CCS. Methods A total exon sequence was used to analyze the possible gene mutations in tumor specimens from patients with CCS. Sanger sequencing was used to verify the presence of suspicious gene mutations in peripheral blood and adjacent tissues. Results the results of total exon sequencing and Sanger sequencing showed that there was a somatic missense mutation c.1061CTP 354L, and the mutation site was the 9th exon of NBN gene. Conclusion: there is a missense mutation of somatic cell on NBN in CCS of c. 1061 CTP 354L. The result of this mutation is that proline is transformed into leucine p. 354L) which leads to the harmful mutation of NBN. The second part is high-throughput sequencing to study the genetic mechanism of mucoepidermoid carcinoma with metastasis of pulmonary myoepithelial carcinoma. Objective to search for the oncogene of mucoepidermoid carcinoma with metastasis of pulmonary myoepithelial carcinoma. Methods the oncogenic mutation of cancer was detected by exon sequencing in patient's tumor sample, and the function of annotation and mutation prediction .2 was used to find the differentially expressed gene set through full transcriptional sequencing. Gene function prediction and pathway annotation .3 were used to find abnormal immune cell molecular markers in patients by immune group library, and the association between immune group library and gene mutation was analyzed. 4. Multisystem bioinformatics analysis was used to analyze the relationship between immune group library and gene mutation. To study the pathogenesis and metastasis of the disease, and to search for drug target combined with immune library. Results (1) according to the possibility of carcinogenesis, the sequence of Driver mutation gene (driven mutation gene was: WNT3, LNC, CCNE1, LC5A4 and so on. The expression of CCNE1 gene was up-regulated from 0.449353809 to 1.411029095. The gene has a specific target drug: ALISERTIBB. Conclusion the mutation of CCNE1 gene may be the cause of carcinogenesis in this case.
【学位授予单位】：中国人民解放军医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R739.87

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