采用高通量测序技术检测肺癌致病突变及靶向药物突变位点

Using high throughput sequencing technology to detect lung cancer pathogenic and drug target mutations

Ion Torrent高通量测序平台可通过测序癌症病人的基因组,找出致病突变位点进而选择对应的靶向药物以更加有效地治疗并减少毒副作用.利用Ion Torrent平台共检测了55例非小细胞肺癌组织的甲醛固定石蜡包埋样本(FFPE样本),对测序结果进行分析并找出致病突变位点.其中,30(54.5%)例样本有抑癌基因TP53的突变,突变类型一共包括36种,是突变频率最高的一个基因.突变频率次高的基因是EGFR,检测到17(30.9%)例病人共8种突变类型.突变频率第三高的是ERBB4(HER4,与EGFR同属HER家族),检测到14(25.5%)例病人共两类突变.此外,还有其他突变频率较高的基因,如MLH1(8例,14.5%)、KRAS(6例,10.9%)、PIK3CA(5例,9.1%)等.本研究表明通过提取肺癌病人FFPE样本中的DNA并使用Ion Torrent平台测序可以找到致病突变,可用于指导医生进行更好的靶向药物治疗.

Cancer is one of the three major killers of human health in the Twenty-first Century, and lung cancer has the highest incidence and mortality. Along with the development of personalized medicine, the treatment oflung cancer is no longer confined to the traditional radiotherapy and chemotherapy. According to the patient＇s individual differences, targeted drugs can effectively treat cancer and reduce side effects. Ion torrent high-throughput sequencing platform can sequence the genome of cancer patients, and then find the causative mutation to select the corresponding targeted therapeutic drugs. We examined the formalin-fixed and paraffin-embedded tissues of 55 cases of non-small cell lung cancer using ion torrent platform, and analyzed the sequencing results to find the pathogenic mutations. Among them, 30（54.5%） samples showed a total of 36 types of mutations in TP53 gene, which had the highest mutation frequency. TP53 is an important tumor suppressor gene that is found to mutate and lose function in a variety of tumors. The second high mutation frequency gene was EGFR, which was detected in 17（30.9%） samples with a total of 8 mutation types. EGFR is a common mutation gene in non-small cell lung cancer, and Gefitinib is an effective targeted therapeutic drug. The third high mutation frequency gene was ERBB4 detected in 14（25.5%） samples with a total of 2 kinds of mutations. ERBB4, also known as HER4, belongs to the same family HER with EGFR. It is also closely related with the occurrence of cancer. Other genes also showed a certain frequency of mutation, including MLH1（8 cases, 14.5%）, KRAS（6 cases, 10.9%）, PIK3CA（5 cases, 9.1%）, in which KRAS mutation has targeted therapeutic drugs, Selumetinib. The results showed that DNA extraction from lung cancer patients FFPE samples and sequencing by ion torrent platform can sort out the mutations to guide doctors in accurate use of targeted therapeutic drugs.