胰腺黏液性囊腺癌基因突变的检测及其临床意义

Detection of gene mutation in pancreatic mucinous cystadenocarcinoma and its clinical significance

目的:利用高通量测序平台研究胰腺黏液性囊腺癌(PMCC)组织中基因突变的分布特点及其临床意义。方法:收集2012年1月至2016年12月经外科手术切除的4例PMCC患者癌及癌旁组织石蜡标本,通过Illumina Hiseq 2500平台进行二代基因测序(NGS),结合患者临床病理资料分析PMCC患者癌组织的基因突变特征。结果:在4个PMCC样本中,均检测到7个高频突变基因(SMG),分别是KRAS、AHNAK2、MUC16、MUC17、MUC19、MUC3A和MUC4。3个样本中检测到24个SMG,分别为ADAMTS9、ALDH3B1、CARD14、CSMD3、MKI67、OR1N2、PKHD1、PLCE1、RTL1、SIGLEC12、CCDC168、CEP295、CUBN、DST、HRNR、LAMA5、OR10G4、OR2T4、PLEKHG4B、RP1L1、SLC15A5、SVEP1、TAS1R1和TNRC18。所有样本中均检测到KRAS驱动基因突变,其中3例检测到KRAS的K12热点突变,另1例检测到KRAS的D33E非热点突变。结论:PMCC患者的高突变KRAS和MUC家族,可能成为PMCC精准治疗的潜在靶点和生物标志物。

Objective:To detect the distribution of gene mutations in pancreatic mucinous cystadenocarcinoma(PMCC)by highthroughput sequencing and to explore its clinical significance.Methods:Four cases of paraffin-embedded cancer tissues and paracancerous tissues from PMCC patients,who underwent surgical resection from January 2012 to December 2016,received NGS(next generation sequencing)examination using Illumina Hiseq 2500 platform.The characteristics of gene mutation in PMCC patients were analyzed with sequencing results and clinicopathological data.Results:Seven significantly mutated genes(SMGs)were detected in all four PMCC samples,namely KRAS,AHNAK2,MUC16,MUC17,MUC19,MUC3 A and MUC4.Twenty-four SMGs were detected in3 of the 4 samples,namely ADAMTS9,ALDH3 B1,CARD14,CSMD3,MKI67,OR1 N2,PKHD1,PLCE1,RTL1,SIGLEC12,CCDC168,CEP295,CUBN,DST,HRNR,LAMA5,OR10 G4,OR2 T4,PLEKHG4 B,RP1 L1,SLC15 A5,SVEP1,TAS1 R1 and TNRC18.KRAS-driven gene mutations were detected in all 4 samples,including K12 hot spot mutation in 3 cases and D33 E non-hot spot mutation in 1 case.Conclusion:The high mutation of KRAS and MUC family in PMCC may be a potential target and biomarker for precise treatment of PMCC.