本文選題：下一代測(cè)序技術(shù) + 原發(fā)性肺肉瘤�。� 參考：《吉林大學(xué)》2017年碩士論文

【摘要】：目的:原發(fā)性肺肉瘤(primary pulmonary sarcoma,PPS)及肺肉瘤樣癌(pulmonary sarcomatoid carcinoma,PSC)均為肺部惡性腫瘤,兩種疾病病理形態(tài)相似,但組織起源不同,治療方法各異。加之兩種疾病的預(yù)后生存不佳,找到基因治療的靶點(diǎn)對(duì)于提高治療效果尤為重要。下一代測(cè)序(next generation sequencing,NGS)技術(shù)是支持巨大通量平行測(cè)序的新一代基因檢測(cè)技術(shù),可對(duì)全基因組、外顯子組和轉(zhuǎn)錄組行全方面測(cè)序。NGS技術(shù)已廣泛應(yīng)用于腫瘤領(lǐng)域研究中。本研究利用NGS技術(shù)對(duì)PPS及PSC患者腫瘤組織進(jìn)行基因檢測(cè),分析兩種疾病突變基因及突變位點(diǎn)的特點(diǎn),找尋可以用于鑒別診斷及作為靶向治療靶點(diǎn)的突變基因,為PPS與PSC的鑒別診斷提供參考,并為其分子靶向治療提供可能。方法:納入2011年6月至2015年6月就診于吉林大學(xué)白求恩第一醫(yī)院胸外科并經(jīng)手術(shù)病理證實(shí)為PPS及PSC的患者。通過(guò)QIAGEN QIAamp DNA Mini Kitt提取患者腫瘤組織DNA。應(yīng)用Ion Torrent PGM平臺(tái)行基因測(cè)序并分析數(shù)據(jù)。獲取高突變基因及新突變位點(diǎn);利用Fisher檢驗(yàn)對(duì)比PPS和PSC的突變基因的差異。結(jié)果:共有8例PPS患者及9例PSC患者被納入該研究。經(jīng)過(guò)基因測(cè)序,PPS中共檢測(cè)出33個(gè)基因的75種突變,共發(fā)現(xiàn)70個(gè)新的突變位點(diǎn)。PSC中共檢測(cè)出29個(gè)基因的273種突變,共發(fā)現(xiàn)229個(gè)新的突變位點(diǎn)。PPS中發(fā)現(xiàn)TP53和BRCA2基因突變患者數(shù)較多。PSC中發(fā)現(xiàn)TP53、BRCA2、NF1及FGFR4基因突變患者數(shù)較多。PPS檢出非共有突變基因16種,PSC檢出非共有突變基因12種。我們對(duì)PPS及PSC共有突變基因中檢出例數(shù)差大于等于2例的NF1、FGFR4基因檢出率行Fisher精確檢驗(yàn),結(jié)果顯示差異均無(wú)統(tǒng)計(jì)學(xué)意義。結(jié)論:PPS及PSC在基因突變上存在各自特點(diǎn),提示利用下一代基因測(cè)序技術(shù)可能從基因水平上鑒別PPS與PSC。PPS及PSC中突變例數(shù)較高的基因突變及新發(fā)現(xiàn)的突變位點(diǎn),可能成為PPS及PSC分子靶向治療靶點(diǎn)。
[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.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R734.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 劉坤;李為民;;原發(fā)性肺肉瘤19例臨床分析[J];中國(guó)肺癌雜志;2012年06期

，

本文編號(hào)：1746154