可切除结直肠癌肺转移的基因特征分析

Genetic characteristics of resectable colorectal cancer with lung metastasis

目的探讨可手术切除结直肠癌(CRC)肺转移与原发性灶基因变异特征。方法收集本院2012—2019年间结直肠癌术后肺转移患者410例的临床资料和33例肺转移灶切除的石蜡包埋组织样品。回顾性分析患者的临床病理资料。采用基于二代测序技术的450 panel基因检测技术分析原发灶/肺转移灶的相关基因,对比每例患者原发灶/肺转移灶的基因图谱变化及变异的总体差异。经质控后纳入最终基因分析的样本量为19例。结果基因检测结果显示原发灶与肺转移灶中最常见的基因变异均为APC、TP53和KRAS。原发灶中检测到更多的基因拷贝数变异(11.4%:4.6%),CRC原发灶与肺转移灶中KRAS基因最常见的位点变异是KRAS G12D。CRC中TP53位点暂无热点变异,肺转移灶与原发灶的TP53位点变异完全一致。10例患者的微卫星状态均为稳定型。原发灶与转移灶肿瘤突变负荷均值相近(5.3 muts/Mb与5.0 muts/Mb,P>0.05)。结论肺转移灶的基因特性与原发肿瘤可能高度一致。KRAS突变可能与CRC患者的肺转移和预后相关。

Objective To investigate the genetic characteristics and prognostic factors of lung metastases and primary tumors that can be surgically removed in colorectal cancer(CRC).Methods The clinical data of 410 patients with lung metastasis from colorectal cancer after operation from January 2012 to July 2019 were collected.Formalin-fixed paraffin-embedded(FFPE)tissue samples of 33 colorectal cancer patients were collected and 19 FFPE samples were for 450 cancer gene next-generation sequencing(NGS)targeted panel assay.Genomic alterations,tumor mutation burden(TMB)values were assessed with a mean coverage of 1000X,including single base substitution,short and long insertion/deletions,copy number variations,gene fusions,and rearrangements.Results Genetic testing results show that the most frequently mutated genes included APC,TP53,and KRAS.We identified the gene amplication variation were enriched at primary tumor.KRAS G12D was the most common alterations.The results showed that there was no hot spot mutation at the TP53 locus in the CRC,and the mutation at the TP53 locus in the metastases was completely consistent with that in primary tumor.The microsatellite status of 10 patients were all stable.The mean TMB of the primary focus was slightly higher than the mean TMB of the metastatic focus((5.3 muts/Mb vs.5.0 muts/Mb,P>0.05).Conclusions Our study revealed that,the genetic characteristics of lung metastases may be highly consistent with the primary tumor.KRAS mutations may be associated with lung metastasis and prognosis in patients with CRC.