基于全外显子测序技术分析胰腺导管癌体细胞突变与患者临床特征的关系  

ASSOCIATION BETWEEN SOMATIC MUTATION AND CLINICAL FEATURES IN PATIENTS WITH PANCREATIC DUCTAL ADENOCARCINOMA BASED ON WHOLE EXOME SEQUENCING

作　　者：宋瑶琳 纪彬彬 刘相兰 杨平[3] 王博 梁乐彬 王爱兰 杨家亮 田埂 邢晓明[1] SONG Yaolin;JI Binbin;LIU Xianglan;YANG Ping;WANG Bo;LIANG Yuebin;WANG Ailan;YANG Jialiang;TIAN Geng;XING Xiaoming(Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266021, China)

机构地区：[1]青岛大学附属医院病理科,山东青岛266021 [2]元码基因科技(北京)股份有限公司 [3]烟台毓璜顶医院病理科

出　　处：《精准医学杂志》2020年第6期471-476,480,共7页Journal of Precision Medicine

基　　金：山东省自然科学基金资助项目(ZR2009CM014);山东省优秀青年科学家基金资助项目(2006BSB14001);青岛民生科技项目(17-3-3-38-nsh)。

摘　　要：目的基于全外显子测序技术分析胰腺导管癌(PDAC)体细胞突变与患者临床特征的关系。方法收集2009—2011年青岛大学附属医院PDAC患者的肿瘤组织样本40例,均进行全外显子组测序。应用肿瘤体细胞突变目录(COSMIC)数据库中的变异单核苷酸多态性(SNP)拟合方法鉴定肿瘤组织中的致癌体细胞突变,并分析致癌体细胞突变与患者临床特征之间的关系。结果PDAC肿瘤组织样本中共检测到1446处致癌体细胞突变位点,每个样本中有25~82处致癌体细胞突变位点;其中体细胞突变类型构成比排名前3位的分别为C>A突变、C>T突变、T>A突变,分别占48%、45%、6%;PDAC肿瘤组织样本中KRAS、RLIM、TTN及BRD9是最常见的突变基因,分别占总突变的42%、33%、26%及22%;不同肿瘤分化程度患者ASTN1基因突变情况差异有显著性(χ^2=6.855,P<0.05),不同肿瘤分期患者TTN基因突变情况差异有显著性(χ^2=5.183,P<0.05)。结论通过与TCGA数据库比对,肿瘤组织样本全外显子测序得到的的致癌体细胞突变谱是较为准确的,利用该突变谱可以有效预测PDAC致癌体细胞突变与患者临床特征之间的关系,从而为PDAC的临床治疗提供指导。Objective\To investigate the association between somatic mutation and clinical features in patients with pancreatic ductal adenocarcinoma(PDAC)based on whole exome sequencing.\Methods\A total of 40 tumor samples were collected from the patients with PDAC who were treated in The Affiliated Hospital of Qingdao University from 2009 to 2011,and whole exome sequencing was performed for all samples.The SNP fitting method in Catalogue of Somatic Mutations in Cancer database was used to identify carcinogenic somatic mutations in tumor tissue,and the association between carcinogenic somatic mutations and clinical features was analyzed.\Results\A total of 1446 carcinogenic somatic mutation sites were detected in PDAC tumor tissue samples,with 25-82 carcinogenic somatic mutations in each sample.C>A mutation was the most common type of somatic mutation(48%),followed by C>T mutation(45%)and T>A mutation(6%),and KRAS was the most common mutant gene(42%),followed by RLIM(33%),TTN(26%),and BRD9(22%).There was a significant difference in ASTN1 gene mutation between the patients with different degrees of tumor differentiation(χ^2=6.855,P<0.05),and there was a significant difference in TTN gene mutation between the patients with different tumor stages(χ^2=5.183,P<0.05).\Conclusion\Comparison with The Cancer Genome Atlas database shows that the spectrum of carcinogenic somatic mutations obtained by whole exome sequencing of tumor tissue samples is proved to be accurate,and such spectrum can be used to effectively predict the association between carcinogenic somatic mutation and clinical features in PDAC patients,which provides guidance for the clinical treatment of PDAC.

关 键 词：胰腺肿瘤 突变 全外显子组测序 病理学 临床 数据库 遗传学 基因检测 

分 类 号：R735.9[医药卫生—肿瘤]