中老年结直肠癌患者POLE、POLD1基因突变分子分型与临床病理特征分析  

Analysis of the molecular typing and clinicopathological features of POLE and POLD1 gene mutations in middle-aged and elderly patients with colorectal cancer

作　　者：王逸菲[1] 何磊[1] 杜俊[1] 崔娣[1] 杨丽[1] 邸婧[1] 刘东戈[1] 王征[1] Wang Yifei;He Lei;Du Jun;Cui Di;Yang Li;Di Jing;Liu Dongge;Wang Zheng(Department of Pathology,Beijing Hospital,National Center of Gerontology,Beijing 100730,China)

机构地区：[1]北京医院病理科国家老年医学中心,北京100730

出　　处：《中华老年医学杂志》2023年第6期701-706,共6页Chinese Journal of Geriatrics

摘　　要：目的探讨携带POLE、POLD1基因突变的中老年结直肠癌患者的临床病理、分子病理改变特征。方法回顾性收集北京医院2020年10月至2022年9月诊断结直肠癌的45岁及以上中老年患者276例,通过二代测序检测及生物信息分析,筛选携带POLE、POLD1基因胚系有害突变及体细胞变异,并将276例患者分为:有害突变组6例,意义不明变异组18例,野生型组252例。同时收集患者的临床、病理特征,分析与其他分子病理检测结果的相关性,包括肿瘤突变负荷(TMB)、微卫星不稳定性状态(MSI)、基因共突变情况等。结果276例结直肠癌患者成功进行二代测序检测,所有患者中未检测出POLE、POLD1基因胚系突变,18例(6.5%,18/276)患者携带POLE基因突变,其中6例(2.2%,6/276)为有害突变,12例(4.3%,12/276)为意义不明变异,余为POLE基因野生型患者。10例(3.6%,10/276)患者携带POLD1基因突变,均为意义不明变异。5例(1.8%,5/276)同时携带两种基因突变。6例有害突变组患者与意义不明变异组及野生型组患者相比显示肿瘤分期早(P<0.05),发生低级别肿瘤出芽现象多见(P<0.05)。而有害突变组及意义不明变异组患者与野生型组患者比较,均更多见于结肠癌患者(P<0.05)及组织学表现低分化组(P<0.05)。有害突变组患者TMB中位数257.76muts/Mb,意义不明变异组患者TMB中位数74.4 muts/Mb,野生型组患者TMB中位数5.81muts/Mb,3组间TMB-H状态比较差异有统计学意义(均P<0.01)。有害突变组、意义不明变异组及野生型组患者检出MSI-H状态分别为1例(16.7%,1/6)、14例(77.8%,14/18)及18例(7.1%,18/276),而意义不明变异组患者MSI-H状态高于野生型组及POLE基因有害突变组患者(均P<0.01)。有害突变组患者KRAS、NRAS、BRAF、PIK3CA基因共突变发生频率高于意义不明变异组及野生型组患者(均P<0.05)。结论有害突变组、意义不明变异组结直肠癌患者存在独特临床病理特征,意义不明变异组�Objective To examine the clinicopathological and molecular pathological characteristics of patients with colorectal cancer(CRC)who have mutations in the POLE and POLD1 genes.Methods In this study,we retrospectively collected data from 276 middle-aged and elderly patients aged 45 years and over who were diagnosed with colorectal cancer at Beijing Hospital between October 2020 and September 2022.We utilized next generation sequencing and bioinformatics analysis to screen for harmful germline and somatic mutations in the POLE and POLD1 genes.The study involved 276 patients,who were divided into three groups based on their genetic mutations.The deleterious mutation group had 6 cases,the mutation of unknown significance group had 18 cases,and the wild type group had 252 cases.We also collected clinical and pathological features of the patients and analyzed their correlation with other molecular pathological results such as tumor mutation burden(TMB),microsatellite instability(MSI),and gene co-mutation.Results No germline mutations were detected in the POLE and POLD1 genes across all patients.Out of the 276 patients,18(6.5%)were found to carry POLE mutations.Among these,6(2.2%)were classified as deleterious mutations,12(4.3%)were positive for POLE mutations of unknown significance,and the remaining patients had wild type POLE genes.Out of the 276 patients,POLD1 gene mutations of unknown significance were found in 10 patients(3.6%).Among the 276 patients,5 cases(1.8%)carried two types of gene mutations.Patients in the deleterious mutation group showed earlier tumor stage(P<0.05)and a higher prevalence of low-grade tumor budding(P<0.05),with 6 patients being affected by this.Compared to the wild type group,colon cancer patients showed a higher frequency of deleterious mutations and variants of unknown significance in the poorly differentiated group(P<o.05).The median TMB in the deleterious mutation group was 257.76 muts/Mb,74.4 muts/Mb in the mutation of unknown significance group,and 5.81 muts/Mb in the wild type group.

关 键 词：结直肠肿瘤 POLE基因 突变 

分 类 号：R735.34[医药卫生—肿瘤]