| Objective: Screen the concomitant drvier genes mutations and their common mutant sites,mutant forms and the concurrent genes by detecting 10 frequent oncogenes in NSCLC.Meanwhile,explore the correlation between concomitant EGFR mutation and clinicopathologic characteristics,acquire the predominant groups,and attain the precision medicine.Methods: We collected 252 NSCLC cases detected by Ion Torrent sequencing and diagnosed by pathology in the First Affiliated Hospital of Dalian Medical University from January 2013 to October 2016,and recorded the genes status and clinical informations all of them,include:1)Clinical data: gender,age,smoking history,family history,clinical TNM staging,multiple primary tumors;2)Pathological features:pathological types and expressions of Ki-67.Results:1.The incidence of diver genes mutationsThe incidence of concomitant genes mutation in NSCLC patients is 23%,and among them,the amount of single site and multi-genes mutations patients is 64%,multi-sites and single gene mutations 19%,multi-sites and multi-genes mutations 17%,with statistical significance(P<0.05).2.The features of driver genes mutations2.1 Type of gene mutations2.1.1 In single site and single gene mutations,incidence of EGFR mutation is67.9%,with statistical significance(P<0.05).2.1.2 KDR(60.7%,P<0.05),TP53(82.6%,P<0.05),PIK3CA(72.7%,P>0.05),KIT(75%,P<0.05),KRAS(55.6%,P>0.05)occur more in single site and multi-genes mutations.2.1.3 BRAF,MET,ROS1 mutations only occur in the type of single site and multi-genes mutations.2.1.4 ALK fusions occur alone.2.2 The sites of concomitant EGFR mutations2.2.1 Single site mutations: The rate of 21 exon missense mutations is 65.2%,with19 exon deletion mutation 30.4%,with statistical significance(P<0.05).2.2.2 Multi-sites mutations: The rate of common mutations with uncommon mutations is 64.3%,with uncommon mutations with uncommon mutations 35.7%,and without common mutations with common mutations,without statistical significance(P>0.05).2.2.3 KDR(29%),TP53(23%)and MET(16%)are more frequent in concomitant EGFR mutations,with statistical significance(P<0.05).2.3 The sites of concomitant KDR mutations2.3.1 Single site mutations: The rate of 7 exon missense mutations is 58.9% with statistical significance(P<0.05).2.3.2 Multi-sites mutations occur in 7 and 11 exons.2.3.3 EGFR(47.7%)and TP53(21%)are more frequent in concomitant KDR mutations,with statistical significance(P<0.05).2.4 The sites of concomitant TP53 mutations2.4.1 Single site mutations: The rate of 5 exon missense mutations is 33.3%,without statistical significance(P>0.05).2.4.2 EGFR(33.3%)and KDR(18.9%)are more frequent in concomitant TP53 mutations,with statistical significance(P<0.05).2.5 The sites of concomitant PIK3 CA mutationsSingle site mutations: The rate of 13 exon missense mutations is 57.1%,without statistical significance(P>0.05).2.6 The sites of concomitant KIT mutations2.6.1 All the single site mutations occur in 10 exon missense mutations.2.6.2 All the multi-sites mutations occur in 10 exon various sites.2.6.3 KDR(37.5%)is the most frequent in concomitant KDR mutations,without statistical significance(P>0.05).2.7 The sites of concomitant KRAS mutationsSingle site mutations: The rate of 2 exon missense mutations is 80%,without statistical significance(P>0.05).2.8 The sites of concomitant BRAF mutationsSingle site mutations: The rate of 11 exon missense mutations is 66.7%,without statistical significance(P>0.05).2.9 MET amplifications are all concurrent with genes mutation,the rate of EGFR is 71.4% without statistical significance(P>0.05).The only one case of ROS1 fusion occurs with MET amplification.3.The correlation between concomitant EGFR mutation and clinical features3.1 The rate of non-smokers is 78.4% with smokers 21.6%,with statistical significance(P<0.05).3.2 The rate of patients without family history is 86.5% and the ones with it 13.5%,with statistical significance(P<0.05).3.3 Mutation rate of stage I patients is 64.9%,with statistical significance(P<0.05).3.4 Higher rate in patients without multiple primary tumor than ones with it(75.7%vs.24.3%,P<0.05).3.5 No correlation with gender and age,without statistical significance(P>0.05).4.The correlation between concomitant EGFR mutation and pathologic features4.1 Concomitant EGFR mutation has correlation with pathologic types,the rate of adenocarcinoma is 78.4%,with statistical significance(P<0.05).4.2 Concomitant EGFR mutation has correlation with adenocarcinoma subgroups,the rate of acinar predominant is 48%,with statistical significance(P<0.05).4.3 There are no significant differences in expression of concomitant EGFR mutationand with single EGFR mutation in the level of Ki-67(P>0.05).5.EGFR mutations have no relevances with KDR,TP53 and MET mutations respectively(P>0.05).Conclusions:1.In the concomitant EGFR mutations,single site mutations mainly occur in 21 exon mutations(P<0.05);multi-sites mutations mostly are common mutations with uncommon mutations(P>0.05).2.In the concomitant EGFR mutations,the common co-altered genes are KDR,TP53,MET(P<0.05),but EGFR mutations have no relevances with KDR,TP53 and MET mutations respectively(P>0.05).3.In the concomitant KDR mutations,7 exon missense mutations are the most common in single site mutations(P<0.05).Multi-sites mutations occur in 7 and 11 exons.EGFR and TP53 mtations are more frequent in concomitant KDR mutations(P<0.05).EGFR and KDR mutations are more frequent in concomitant TP53 mutations(P<0.05).4.Concomitant EGFR mutations have correlations with non-smokers,no family history,without multiple primary tumors(P<0.05),but no correlations with gender or age(P>0.05).5.Concomitant EGFR mutation has correlation with pathologic types,the rate of adenocarcinoma is 78.4%,with statistical significance(P<0.05).Concomitant EGFR mutation has correlation with adenocarcinoma subgroups,the rate of acinar predominant is 48%,with statistical significance(P<0.05).6.There are no significant differences in expression of concomitant EGFR mutation and with single EGFR mutation in the level of Ki-67(P>0.05). |
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