二代测序获得胰腺癌患者肿瘤相关基因变异图谱分析

Tumor-related Gene Mutation Profile of Pancreatic Cancer Detected with Second Generation Sequencing

[目的]了解胰腺癌患者的基因变异情况,为胰腺癌的个体化治疗提供探索依据。[方法]收集58例原发胰腺恶性肿瘤患者,利用二代基因测序技术(NGS)检测肿瘤组织和体细胞的基因变异情况,绘制基因变异图谱,并结合临床资料进行分析。[结果] 53例胰腺腺癌患者中最常见的突变基因是KRAS、TP53、CDKN2A、SMAD4、ARID1A、RNF43 (突变发生频率在10%以上)等。原发灶和转移灶、不同性别的样本之间,基因变异基本相似。肿瘤相关重要通路,如MAPK通路变异89.0%,G1/S通路变异84.9%,HRD相关通路变异17.0%,TGF-β信号通路变异35.8%,SWI/SNF复合物通路变异46.0%。其中54.7%的患者至少有1个潜在可用药靶点。免疫生物标志物方面高肿瘤突变负荷(TMB-H)占1/52(1.9%),可分析的52例患者全部为微卫星稳定(MSS)。[结论]该研究中胰腺癌患者的全肿瘤相关基因测序情况,在主要的突变基因和潜在可用药靶点基因上,与国外报道相似,少数低频率突变的基因差异有待扩大样本量进一步验证。超50%的患者存在潜在可用药靶点,为胰腺癌的靶向免疫治疗提供了个体化治疗依据。

[Purpose]To detect the tumor-related gene mutations of pancreatic cancer.[Methods]Tissue and blood samples were collected from 58 patients with primary pancreatic carcinoma.The gene mutation profile of tumor tissues was detected with the next generation sequencing(NGS),and the clinical data was analyzed.[Results]KRAS,TP53,CDKN2A/B,SMAD4,ARID1A and RNF43 were the most common mutations in the 53 cases of pancreatic adenocarcinoma.The distribution of gene variations was similar between primary and metastatic lesions,also between male and female patients.About the important tumor regulatory pathways,there were 89.0%of patients containing variations of MAPK pathway,84.9%variations of G1/S pathway,17.0%variations of homologous recombination defect(HRD)related pathway,35.8%variations of TGF-βsignaling pathway,and46.0%variations of SWI/SNF complex pathway.About 54.7%of these patients had at least one potential drug target.High tumor mutational burden(TMB-H)(1/52,1.9%)was detected in terms of immunoassay points,all patients were microsatellite stability(MSS)(52/52).[Conclusion]In terms of the major mutant genes and potential drug target genes,the genomic landscape of pancreatic cancer patients in the study is similar to that as reported in literature.The differences of a few lowfrequency mutations need to be further verified by expanding the sample size.More than 50%of patients have potential actionable mutations,which provide a basis for individualized treatment of pancreatic cancer.