基于下一代测序技术的原发性肺肉瘤及肺肉瘤样癌的基因突变研究

发布时间：2018-04-13 20:55

本文选题：下一代测序技术 + 原发性肺肉瘤　；参考：《吉林大学》2017年硕士论文

【摘要】：目的:原发性肺肉瘤(primary pulmonary sarcoma,PPS)及肺肉瘤样癌(pulmonary sarcomatoid carcinoma,PSC)均为肺部恶性肿瘤,两种疾病病理形态相似,但组织起源不同,治疗方法各异。加之两种疾病的预后生存不佳,找到基因治疗的靶点对于提高治疗效果尤为重要。下一代测序(next generation sequencing,NGS)技术是支持巨大通量平行测序的新一代基因检测技术,可对全基因组、外显子组和转录组行全方面测序。NGS技术已广泛应用于肿瘤领域研究中。本研究利用NGS技术对PPS及PSC患者肿瘤组织进行基因检测,分析两种疾病突变基因及突变位点的特点,找寻可以用于鉴别诊断及作为靶向治疗靶点的突变基因,为PPS与PSC的鉴别诊断提供参考,并为其分子靶向治疗提供可能。方法:纳入2011年6月至2015年6月就诊于吉林大学白求恩第一医院胸外科并经手术病理证实为PPS及PSC的患者。通过QIAGEN QIAamp DNA Mini Kitt提取患者肿瘤组织DNA。应用Ion Torrent PGM平台行基因测序并分析数据。获取高突变基因及新突变位点;利用Fisher检验对比PPS和PSC的突变基因的差异。结果:共有8例PPS患者及9例PSC患者被纳入该研究。经过基因测序,PPS中共检测出33个基因的75种突变,共发现70个新的突变位点。PSC中共检测出29个基因的273种突变,共发现229个新的突变位点。PPS中发现TP53和BRCA2基因突变患者数较多。PSC中发现TP53、BRCA2、NF1及FGFR4基因突变患者数较多。PPS检出非共有突变基因16种,PSC检出非共有突变基因12种。我们对PPS及PSC共有突变基因中检出例数差大于等于2例的NF1、FGFR4基因检出率行Fisher精确检验,结果显示差异均无统计学意义。结论:PPS及PSC在基因突变上存在各自特点,提示利用下一代基因测序技术可能从基因水平上鉴别PPS与PSC。PPS及PSC中突变例数较高的基因突变及新发现的突变位点,可能成为PPS及PSC分子靶向治疗靶点。
[Abstract]:Objective: primary pulmonary sarcoma (PPS) and pulmonary sarcomatoid carcinoma (PSC) are pulmonary malignant tumors. The pathological morphology of the two diseases is similar, but the tissue origin is different and the treatment methods are different.Moreover, the prognosis of the two diseases is poor, so it is very important to find the target of gene therapy to improve the therapeutic effect.The next generation generation sequencing technique is a new generation of gene detection technology that supports large throughput parallel sequencing. It can be used in the whole genome, exon group and transcription.NGS technology has been widely used in cancer research.In this study, NGS technique was used to detect the tumor tissues of PPS and PSC patients, and to analyze the characteristics of mutation genes and mutation sites of the two diseases, and to find the mutated genes that could be used for differential diagnosis and target therapy.To provide a reference for differential diagnosis of PPS and PSC, and to provide the possibility of molecular targeted therapy.Methods: from June 2011 to June 2015, the patients who were admitted to the Department of Thoracic surgery of Bai Qiuen first Hospital of Jilin University and proved to be PPS and PSC surgically and pathologically.The tumor tissue was extracted by QIAGEN QIAamp DNA Mini Kitt.Ion Torrent PGM platform was used for gene sequencing and data analysis.The high mutation gene and the new mutation site were obtained, and the differences between PPS and PSC mutation genes were compared by Fisher test.Results: a total of 8 patients with PPS and 9 patients with PSC were included in the study.A total of 75 mutations of 33 genes were detected by sequencing PPS, and 273 mutations of 29 genes were detected by PSC.A total of 229 new mutations were found in PPS. The number of patients with TP53 and BRCA2 gene mutations was higher. TP53, BRCA2NF-1 and FGFR4 gene mutations were found in more patients. PPS detected 16 non-co-mutant genes and 12 non-co-mutant genes.The detection rate of NF1 FGFR4 gene in PPS and PSC co-mutation genes with the difference greater than or equal to two cases was detected by Fisher. The results showed that there was no significant difference in the detection rate of NF1 FGFR4 gene.Conclusion PSC and PPS have their own characteristics in gene mutation, suggesting that the next generation gene sequencing technique may be used to identify the high number of mutations and newly discovered mutation sites in PPS, PSC.PPS and PSC at the gene level.It may be a target of PPS and PSC targeted therapy.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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