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Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,精准医学（肿瘤领域）检测方案设计和质控,基于新一代测序（,NGS,）的肿瘤精准医学检测产品设计,全球多中心数据整合和数据质控,基于,iFISH-CTC,技术的单细胞测序临床应用,肿瘤早期检测,肿瘤个体化诊疗方案,整合国际肿瘤数据库的基因,Panel,设计与应用,超高深度基因测序,Panel,的设计,肿瘤负荷、继发耐药监控,1,精准医学（肿瘤领域）检测方案设计和质控,基于新一代测序（,NGS,）的肿瘤精准医学检测产品设计,全球多中心数据整合和数据质控,2,新一代测序平台互补融合性,不同测序仪平台可以使用不同基因富集方法,PCR,捕获,PCR,捕获,Ion,Ion,Illumina,Illumina,3,基因变异类型检测,I,：突变,基因全长（全外显子）的所有点突变,影响因素：基因富集覆盖度（,90%,）,影响因素：测序深度（,200X,）,报告中的突变,%,灵敏度：,1%,4,临床研究发现癌组织中,CNV,及,Mutation,共存,肿瘤分型新概念,（,C,型肿瘤，,M,型肿瘤）,2015,年,CSCO,年会厦门,基因变异类型检测,II,：拷贝数变异,（,Copy Number Variation, CNV,）,5,基因变异类型检测,III,：融合基因,NGS,检测融合基因,RNA,转录混合法,NCI-MATCH Sample Test,-Oncomine Comprehensive Panel,6,肿瘤发病机制学说,肿瘤的器官发生学说,肿瘤的血液发生学说,肿瘤的,泛感染发生学说,及诊疗进展,50,例接受缬更昔洛韦（,Valcyte,）治疗的胶质母细胞瘤患者,2,年生存率为,62%,，对照组为,18%,（,P0.001,）。治疗周期长的亚组预后更好，,2,年生存率可达,70%,和,90%,上海,xx,医院使用,xxx,抗病毒药物治疗,xxx,瘤获得突破性进展,N Engl J Med 2013 Sep 5;369(10):985-6,7,8,基于,iFISH-CTC,技术的单细胞测序临床应用,肿瘤早期检测,肿瘤个体化诊疗方案,iFISH-CTC,技术,助力肿瘤精准医学研究,9,肿瘤早期,iFISH-CTC,检测数据,（）,5363,例统计,癌种,灵敏度,乳腺癌,95.93%,结直肠癌,93.18%,肝癌,81%,胰腺癌,97.73%,肺癌,91.67%,胃癌,92.59%,甲状腺癌,87%,食管癌,81.8%,10,2015,年,CSCO,年会厦门,癌症早期筛查,受检者信息,检测路径,病理检查,结果：低分化腺癌,手术切除腺癌,11,12,肿瘤早期综合检测及预防案例,-,福建,x,州,xx,医院,循环肿瘤细胞检测,体内存在肿瘤细胞,提示癌组织特征及用药指导,发现,22,个,肿瘤细胞,影像学显示右肺弥漫状阴影,（纤维化,/,癌变）,激光显微切割,单个,CTC,肿瘤细胞,单细胞全基因组,测序分析,1,2,3,4,5,定期随访和复查,6,癌标,NSE,：,72.6,（, 99%,每份样本测序深度,10000X,19,Phase 1 results,1,262,HCC,related somatic mutations,from original file (3,000,381 somatic mutations in total, for all phenotypes).,425 non-redundant HCC related somatic mutations, with unique genomic coordinates.,These 425 mutations reside in,36,exons (covering,28,genes).,Results would also be shown in figures later.,20,Phase 1 results,The covered,28,genes are (by official symbol):,AACS,ADAM22,AKAP13,ARVCF,ATR,CDKN2A,CLCC1,CUL3,DMGDH,EGFR,ERBB2,GABBR1,GIF,GTPBP2,HNF1A,JAK2,LITAF,MET,MFSD8,MUC5B,MYCL,NOVA1,NTRK2,PCDH7,PLEKHG5,PSTK,RAF1,USP25.,OR (by ensembl ID):,ENSG00000008277.10,ENSG00000036257.8,ENSG00000081760.12,ENSG00000096968.8,ENSG00000099889.9,ENSG00000105976.10,ENSG00000116990.9,ENSG00000117983.13,ENSG00000121940.11,ENSG00000132155.7,ENSG00000132837.10,ENSG00000134812.3,ENSG00000135100.13,ENSG00000139910.15,ENSG00000141736.9,ENSG00000146648.11,ENSG00000147889.12,ENSG00000148053.11,ENSG00000155313.11,ENSG00000164073.5,ENSG00000169851.11,ENSG00000170776.15,ENSG00000171680.16,ENSG00000172432.14,ENSG00000175054.10,ENSG00000179988.9,ENSG00000189067.8,ENSG00000204681.6,21,Phase 1 Results,These,36,exons covered,12,415bp,in total, including:,chr1 2061bp,chr2 97bp,chr3 201bp,chr4 3218bp,chr5 249bp,chr6 322bp,chr7 621bp,chr8 0bp,chr9 1986bp,chr10 282bp,chr11 350bp,chr12 540bp,chr13 0bp,chr14 1400bp,chr15 136bp,chr16 157bp,chr17 342bp,chr18 0bp,chr19 0bp,chr20 0bp,chr21 325bp,chr22 128bp,chrX 0bp,chrY 0bp,22,6-phase selector,Method description:,Phase 2,:,max coverage,“For each exon with SNVs covering 5 patients in LUAD and SCC, we selected the exon with highest RI that identified at least 1 new patient when compared to the prior phase.”, original paper,Data required:,TCGA,maf files (somatic mutation),23,6-phase selector,Method description:,Phase 3,: RI = 30 & =3 patients,“For each remaining exon with an RI 30 and with SNVs covering 3 patients in LUAD and SCC, we identified the exon that would result in the largest reduction in patients with only 1 SNV.”, original paper,Data required:,TCGA,maf files (somatic mutation),24,6-phase selector,Method description:,Phase 4,: RI = 20 & = 3 patients,“Same procedure as phase 3, but using RI 20.”, original paper,Data required:,TCGA maf files (somatic mutation),25,6-phase selector,Method description:,Phase 5,:,Predicted drivers,“We included all exons from additional genes previously predicted to harbor driver mutations in NSCLC.”, original paper,Data required:,predicted driver gene in HCC (from publication, 15 genes in,reference paper,),26,6-phase selector,Method description:,Phase 6,:,Add fusions,“For recurrent rearrangements in NSCLC involving the receptor tyrosine kinases ALK, ROS1, and RET, the introns most frequently implicated in the fusion event and the flanking exons were included.”, original paper,Not included (not under our consideration by far).,27,Results,This panel includes:,604 genes (not necessarily have all exons of this gene included in panel),782 exons,120.1 kb in total, 154 bp per exon,202 patients in total,199 patients covered by this panel,199 (99%), 181 (90%), 158 (78%) patients with at least 1, 2, 3 SNVs,Mean RI is 22.67 (Recurrence Index, the higher this number the more chance a SNV is found in patients),RI is 2.23, 68.85, 38.47, 23.52, 1.04 for phase 1, 2, 3, 4, 5,28,Results shown by figures,29,30,In original paper the total patient number is 407, for us this number is only 202.,31,Fig1b From original paper,32,Data summary,33,
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