1、精准医学（肿瘤领域）检测方案设计和质控精准医学（肿瘤领域）检测方案设计和质控 基于新一代测序（基于新一代测序（NGS）的肿瘤精）的肿瘤精准医学检测产品设计准医学检测产品设计 全球多中心数据整合和数据质控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IonIonIlluminaIllumina3基因变异类型检测基因变异类型检测 I：突变：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临床研究发
2、现癌组织中CNV及及Mutation共存共存肿瘤分型新概念肿瘤分型新概念（C型肿瘤，型肿瘤，M型肿瘤）型肿瘤）2015年年CSCO年会厦门年会厦门 基因变异类型检测基因变异类型检测 II：拷贝数变异：拷贝数变异（Copy Number Variation,CNV）5基因变异类型检测基因变异类型检测 III：融合基因：融合基因 NGS检测融合基因 RNA转录混合法NCI-MATCH Sample Test -Oncomine Comprehensive Panel6肿瘤发病机制学说肿瘤发病机制学说 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泛感染发生学说及诊疗进展 50例接受缬
3、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):985-67基于基于iFISH-CTC技术的单细胞测序临床应用技术的单细胞测序临床应用肿瘤早期检测肿瘤早期检测 肿瘤个体化诊疗方案肿瘤个体化诊疗方案8iFISH-CTC技术技术助力肿瘤精准医学研究助力肿瘤精准医学研究9肿瘤早期肿瘤早期iFISH-CTC检测数据检测数据（2014.1-2015.8）5363例统计癌种癌种灵敏
4、度灵敏度乳腺癌 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%102015年年CSCO年会厦门年会厦门 癌症早期筛查受检者信息检测路径病理检查病理检查结果：低分化腺癌结果：低分化腺癌手术切除腺癌手术切除腺癌11肿瘤早期综合检测及预防案例肿瘤早期综合检测及预防案例 -福建福建x州州xx医院医院循环肿瘤细胞检测循环肿瘤细胞检测体内存在肿瘤细胞提示癌组织特征提示癌组织特征及用药指导及用药指导发现 22 个肿瘤细胞影像学显示右肺弥影像学显示右肺弥漫状阴影漫状阴影（纤维化（纤维化/癌变）癌变）激光显微切割激光显微切割单个单个C
5、TC肿瘤细肿瘤细胞胞单细胞全基因组单细胞全基因组测序分析测序分析12345定期随访和复查定期随访和复查6癌标癌标NSE：72.6（99%每份样本测序深度每份样本测序深度10000X19Phase 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.
6、These 425 mutations reside in 36 exons(covering 28 genes).Results would also be shown in figures later.20Phase 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,PC
7、DH7,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,ENSG000001399
8、10.15,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,ENSG00000204681.621Phase 1 Results These 36 exons c
9、overed 12,415bp in total,including:chr1 2061bp chr2 97bp chr3 201bp chr4 3218bp chr5 249bp chr6 322bp chr7 621bp chr8 0bp chr9 1986bp chr10 282bpchr11 350bpchr12 540bpchr13 0bpchr14 1400bpchr15 136bpchr16 157bpchr17 342bpchr18 0bpchr19 0bpchr20 0bpchr21 325bpchr22 128bpchrX 0bpchrY 0bp226-phase sele
10、ctorMethod 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 paperData required:TCGA maf files(somatic mutation)236-phase selectorMethod
11、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 paperData required:TCGA maf files(somatic mutation)246-phase selector
12、Method description:Phase 4:RI=20&=3 patients “Same procedure as phase 3,but using RI 20.”original paperData required:TCGA maf files(somatic mutation)256-phase selectorMethod description:Phase 5:Predicted drivers “We included all exons from additional genes previously predicted to harbor driver mutat
13、ions in NSCLC.”original paperData required:predicted driver gene in HCC(from publication,15 genes in reference paper)266-phase selectorMethod description:Phase 6:Add fusions “For recurrent rearrangements in NSCLC involving the receptor tyrosine kinases ALK,ROS1,and RET,the introns most frequently im
14、plicated in the fusion event and the flanking exons were included.”original paperNot included(not under our consideration by far).27Results 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 19
15、9 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 1,2,3,4,528Results shown by figures2930In original paper the total patient number is 407,for us this number is only 202.31Fig1b From original paper32Data summary33Thank You世界触手可及世界触手可及携手共进，齐创精品工程携手共进，齐创精品工程
