Research On The Detection Of Gene Mutation In ICC By Next-generation Sequencing

Objective Through the complete sequence analysis of tumor tissue and blood cells genomes of patients with intrahepatic cholangiocarcinoma,the gene variation information of tumor tissues and blood cells of patients with intrahepatic cholangiocarcinoma was obtained,and the gene variation information of patients with intrahepatic cholangiocarcinoma was identified for tumor molecular typing.The correlation between the type of gene mutation and prognosis was statistically analyzed in order to provide valuable information for stratified and individualized diagnosis and treatment of intrahepatic cholangiocarcinoma.Method 63 patients with cholangiocarcinoma diagnosed pathologically after radical resection were collected from December 2017 to December 2020.The patients were selected for possible mutations(mutation,copy number change,gene fusion,etc.)by full exon Next generation gene sequencing(NGS),Tumor gene mutation molecular typing and follow-up statistical analysis of TP53 gene mutation.Whether there is statistical difference in disease-free survival(DFS)between patients with CDKN2 A gene mutation and patients with both CDKN2 A and TP53 gene mutations,and to analyze the relationship between gene mutation types and gene variation and prognosis.Results1.Total exon sequencing of cancer tissues and blood cells from 63 patients with ICC who underwent radical surgery showed that a total of541 gene changes were found in 63 samples.The five genes with the most mutations in ICC patients were: TP53 gene with a mutation rate of42.9%(27/ 63);KRAS gene with a mutation rate of 33.3%(21/63);CDKN2A gene with a mutation rate of 23.8%(15/63);and ARID1 A gene with a mutation rate of 20.6%(13/ 63);TERT gene with a mutation rate of 15.9%(10/ 63).The test results also found that there were potential copy number variants of carcinogenic sites in several genes,such as amplification of FRS2(4.7%),MDM2(4.7%),CDK12(3.2%),ERBB2(3.2%);deletion of RMB10(11.1%),PBRM1(6.3%),BAP1(6.3%),TGFBER2(6.3%),and rearrangement of FGFR2(4.7%).2.The 1-DFS survival rate of patients with TP53 gene mutation was36.8%,the median DFS was 9.0 months,the 95%CI was(5.83-12.17),the1-DFS survival rate of patients with CDKN2 A gene mutation was 56.3%,the median DFS was 15.0 months,95%CI(6.32-23.68).The 1-DFS survival rate of patients with both TP53 and CDKN2 A gene mutations was 25.0%,with a median DFS of 7.0 months;95%CI(3.08-10.92).Conclusion1.The molecular types of common mutant genes in patients with intrahepatic cholangiocarcinoma include TP53,KRAS,CDKN2 A,ARID1A,and TRET.2.In addition to the common base mutations,gene mutations in patients with intrahepatic cholangiocarcinoma include the amplification of gene copy number of FRS2,MDM2,CDK12,ERBB2;the deletion of RMB10,PBRM1,BAP1 and TGFBER2,and the rearrangement of FGFR2.3.The prognosis of patients with TP53 gene mutation was poorer than that of patients with CDKN2 A gene mutation;there was no significant difference in prognosis between patients with TP53&CDKN2A gene mutation and patients with TP53 gene mutation;and patients with both TP53&CDKN2A gene mutation was worse than those with CDKN2A gene mutation.4.The prognosis of patients with intrahepatic cholangiocarcinoma is related to the molecular type of gene mutation in their cancer tissues.