你所需,我所有-肿瘤液体活检方案有Thermo Fisher就够%

Proprietary&

Confidential你所需，我所有——肿瘤液体活检方案有Thermo

Fisher就够了12©2016ThermoFisherScientificCorporation.Allrights

reserved.MoleculartestingguidelinesforinformingtreatmentoptionsforNSCLCpatients,asrecommendedbyCAP1,AMP1,IASLC1,and

NCCN2:EGFR,ALK,ROS1,BRAF,andPDL1testingforfirst-line

therapies2Emergingtargetedagentsforpatientswithothergeneticalterations,includingKRAS,HER2,MET,

andRET2Broadermolecularprofilingtoidentifyraredrivermutationsforwhicheffectivedrugsmaybealreadyavailable,ortoappropriatelycounselpatientsregardingtheavailabilityofclinicaltrials;broad

molecularprofilingisakeycomponentoftheimprovementtocareofpatientswith

NSCLC2多基因检测为相关指南所推荐精准治疗方案的制定离不开多基因检测，多种相关指南均建议实体肿瘤患者可尝试多基因检测。Journalof

Molecular

Diagnostics,

Molecular

Testing

Guideline

for

Selection

of

Lung

Cancer

Patientsfor

EGFR

and

ALK

Tyrosine

Kinase

Inhibitors.

Guideline

from

the

College

of

American

Pathologists,

International

Association

for

the

Study

of

L

ung

Cancer,

and

Association

for

Molecular

Pathology

15(4),

July

2013.NCCNClinicalPracticeGuidelinesinOncology(NCCNGuidelines™),Non-SmallCellLungCancer,v8.2017,NCCN.org.Forinvitrodiagnostic

use.2©2016ThermoFisherScientificCorporation.Allrights

reserved.实时的肿瘤分子分型有助于选择最为合适的治疗策略Therapy

1Therapy

2Therapy

3EGFR

Exon

19 EGFRExon19

(20%) EGFRExon19

(29%) EGFRExon19

(20%)KRAS

p.G13D

(55%) T790M

(6%) T790M

(2%)MET

p.N375S

(40%) P53

p.G245V

(10%) P53p.G245V

(3%)MET

p.T1010I

(20%) MET

p.N375S

(59%) METp.N375S

(55%)BaselineTime1TBB/TTBTime

2Pleuraerguss

(90%)Time

3Liquidbiopsy

(ctDNA)EGFR(Exon

19)肿瘤分子分型的时空特异性治疗压力可能会导致肿瘤发Th变异，产Th耐药突变或者驱动基因的改变3ForResearchUseOnly.Notforuseindiagnostic

procedures3©2016ThermoFisherScientificCorporation.Allrights

reserved.液体活检可作为组织活检的有效补充液体活检非侵入性的实时取样：为需要实时监控疗效的靶向治疗患者提供耐药监测的可能取样容易：为无手术样本或难以穿刺的肿瘤患者提供精准靶向治疗方案的可能4ForResearchUseOnly.Notforuseindiagnostic

procedures4©2016ThermoFisherScientificCorporation.Allrights

reserved.NCCN

Guideline和CSCO指南的建议中国临床肿瘤学会（CSCO）原发性肺癌诊疗指南

2017.V15ForResearchUseOnly.Notforuseindiagnostic

procedures5©2016ThermoFisherScientificCorporation.Allrights

reserved.液体活检的临床意义治疗方案选择疗效监控复发监控血液样本、手术样本及术后三天样本3

weeks

为周期取样，持续6-8轮3-6个月为周期取样Solid

tumorsample中等灵敏度价格适中高灵敏度低价最高灵敏度低价市场需求适用平台肿瘤患者疾病周期一代测序：组织NGS(0.1%to1%

LOD)：组织

&血液数字PCRNGS(0.1%

LOD)数字PCRNGS(0.1%

LOD)Liquid

biopsysample早期诊断(Screening)Liquid

biopsysample血液样本高灵敏度低价NGS(large

pan-cancer

panels)*PiperJaffray,The2015LiquidBiopsyReport,September

20156ForResearchUseOnly.Notforuseindiagnostic

procedures6©2016ThermoFisherScientificCorporation.Allrights

reserved.对检测灵敏度要求高cfDNA中样本间差异大，早期患者ctDNA的含量低对检测灵敏度要求高 ctDNA丰度变化大ctDNA突 变比例低检测目的

不同

需要不同的检测方案定性

or

定量单基因or多基因检测结果

解读需要医学的解读需要相应指南规范解读液体活检所面临的挑战7ForResearchUseOnly.Notforuseindiagnostic

procedures7©2016ThermoFisherScientificCorporation.Allrights

reserved.最接近临床转化的NGS液体活检应用治疗方案选择疗效监控复发监控血液样本、手术样本及术后三天样本3

weeks

为周期取样，持续6-8轮3-6个月为周期取样Solid

tumorsample中等灵敏度价格适中高灵敏度低价最高灵敏度低价市场需求适用平台肿瘤患者疾病周期一代测序：组织NGS(0.1%to1%

LOD)：组织

&血液数字PCRNGS(0.1%

LOD)数字PCRNGS(0.1%

LOD)Liquid

biopsysample早期诊断(Screening)Liquid

biopsysample血液样本高灵敏度低价NGS(large

pan-cancer

panels)*PiperJaffray,The2015LiquidBiopsyReport,September

20158ForResearchUseOnly.Notforuseindiagnostic

procedures8©2016ThermoFisherScientificCorporation.Allrights

reserved.Oncomine™液体活检试剂盒：一管血实现多基因0.1%低频突变检测肺癌LungcfDNA

Assay11

genesHotspots肺癌LungcfTNA

Assay12genesDNAand

RNAHotspotsCNVs,

Fusion泛癌种Pan-cancercfTNA

Assay52genesDNAandRNAHotspots,

CNVsFusions,

TumorSuppressor乳腺癌BreastcfDNAAssay

v212

genesHotspotsCNVsTP53结直肠癌ColoncfDNA

Assay14

genesHotspots乳腺癌BreastcfDNA

Assay10

genesHotspots9ForResearchUseOnly.Notforuseindiagnostic

procedures9©2016ThermoFisherScientificCorporation.Allrights

reserved.晚期驱动基因阳性NSCLC的液体活检：治疗方案选择及耐药检测中国临床肿瘤学会（CSCO）原发性肺癌诊疗指南

2017.V110©2016ThermoFisherScientificCorporation.AllrightsreservedF.orResearchUseOnly.Notforuseindiagnostic

procedures10©2016ThermoFisherScientificCorporation.Allrights

reserved.Oncomine™

lung

cfTNAAssay：NSCLC突变、融合和CNV液体活检cfDNA&cfRNAIonTorrent™Oncomine™Lung

Cell-FreeTotalNucleicAcidResearch

Assay(单个文库)ALKBRAFEGFRERBB2KRASMAP2K1METNRASPIK3CARETROS1TP53125811>169GenesAmpliconsGeneswithkeyhotspot

mutationsHotspotSNVsand

indels49Fusions:ALK，RET,

ROS1基因突变类型靶向药物EGFRExon18-21

突变（敏感&耐药）吉非替尼、厄洛替尼、埃克替尼、阿法替尼、达克替尼、奥希替尼ALK融合（敏感）/突变（耐药）克唑替尼、色瑞替尼、艾乐替尼、Brigatinib、LorlatinibROS1融合（敏感）克唑替尼BRAFV600E（敏感）达拉非尼联合曲美替尼MET扩增/14外显子跳跃突变（敏感）克唑替尼、沃利替尼（和记黄埔，临床阶段）ERBB2（HER2）Exon20突变（敏感）阿法替尼RET融合（敏感）卡博替尼、凡德他尼KRAS/NRASG12X,

G13X,

Q61X

（耐药）不合适用TKISNVLODdownto0.1%with20nginput,samesensitivityand

specificityFusions:ALK，RET,ROS1—at1%

LODCNVMET，METexon14

skipping11©2016ThermoFisherScientificCorporation.Allrights

reserved.IV期结直肠癌治疗方案药物作用机制基因检测贝伐珠单抗（安维汀）联合5-氟尿嘧啶（化疗）抗血管Th成（VEGF）无西妥昔单抗（爱必妥）/帕尼单抗联合伊立替康（化疗）抑制表皮Th长因子（EGFR）KRAS/NRAS/BRAF（野Th型敏感）帕母单抗/纳武单抗抑制PD-1与PD-L1结合（免疫治疗）dMMR（DNA错配修复基因缺陷）MSI-H（微卫星不稳定）晚期结直肠癌的治疗方案结直肠癌靶向治疗耐药检测Prevalenceofgeneticalterationsassociatedwithdenovoresistancetoanti-EGFRtherapiesin

mCRC.结直肠癌96%的靶向治疗（西妥昔单抗和帕尼单抗）耐药发Th与KRAS，NRAS，BRAF，EGFR的突变相关

；EGFR胞外结构域的变体（s492r）提示患者会对西妥昔单抗治疗产Th抗性，对帕尼单抗治疗则不然；SandraMisaleetal.CancerDiscovery

2014;4:1269-128012©2016ThermoFisherScientificCorporation.Allrights

reserved.晚期结直肠癌的靶向治疗：CSCO指南2017版13©2016ThermoFisherScientificCorporation.Allrights

reserved.Oncomine™

Colon

cfDNAAssay：结直肠癌液体活检NCCN推荐检测的耐药基因Oncomine™

cfDNA

Colon

Cancer

Assay涵盖热点突变治疗方案KRASp.A146Tp.Q61Hp.Q61Lp.Q61Rp.G13Dp.G13Cp.G12A

p.G12Dp.G12Fp.G12Vp.G12Cp.G12R

p.G12S野Th型：化疗+帕尼单抗/西妥昔单抗（爱必妥）NRASp.Q61Lp.Q61Rp.Q61Kp.G13Vp.G13Ap.G13Dp.G13Np.G13Vp.G13Yp.G13Cp.G13Rp.G13Sp.G12Ep.G12Ap.G12D

p.G12Np.G12Pp.G12Vp.G12Yp.G12Cp.G12R

p.G12S野Th型：化疗+帕尼单抗/西妥昔单抗（爱必妥）BRAFp.V600Ep.L597V

p.D594G野Th型：化疗+帕尼单抗/西妥昔单抗（爱必妥）PIK3CAp.E542Kp.E545Kp.E545Qp.E545Gp.Q546Kp.Q546P

p.Q546Rp.M1043Vp.M1043Ip.H1047Yp.H1047Lp.H1047R

p.G1049R野Th型：化疗+帕尼单抗/西妥昔单抗（爱必妥）Panel设计 热点突变基因（14基因）涵盖基因KRAS,NRAS,BRAF,

PIK3CAAKT1,CTNNB1,EGFR,ERBB2,FBXW7,GNAS,MAP2K1,SMAD4,

TP53,APC14©2016ThermoFisherScientificCorporation.Allrights

reserved.乳腺癌分子亚型病理系统性辅助治疗Luminal

（管腔或激素受体阳性）A型ER+和（或）PR+Ki67低表达（<15%）内分泌治疗为主

化疗Luminal（管腔或激素受体阳性）

B型HER2过表达型ER+和（或）PR+Her2-Ki67高表达（≥15%）内分泌治疗±细胞毒治疗ER+和（或）PR+Her2+Ki67高表达（≥15%）细胞毒治疗+内分泌治疗+抗HER2靶向治疗ER-

PR-Her+细胞毒治疗+抗HER2靶向治疗基底样性ER-

PR-Her2-细胞毒治疗BRCA突变患者：PARP抑制剂，如奥拉帕尼不同分子亚型乳腺癌的辅助治疗方案选择15©2016ThermoFisherScientificCorporation.Allrights

reserved.Oncomine™

Breast

cfDNA

Assay：乳腺癌突变和CNV液体活检cfDNAIonTorrent™Oncomine™BreastcfDNAResearchAssayv2(单管检测)AKT1CCND1EGFRERBB2ERBB3ESR1FBXW7FGFR1KRASPIK3CASF3B1TP53127610>152GenesAmpliconsGeneswithkeyhotspotmutationsHotspotSNVsand

indelsSNVLODdownto0.1%with20nginputsamesensitivityand

specificityCNVsCCND1,ERBB2,FGFR1detectfoldchangeof

1.2–1.4xTP53Morecompletecoverage;0.5%LODondenovo

sequencing基因突变类型靶向药物ERBB2（HER2）扩增曲妥珠单抗（赫赛汀）、拉帕替尼、帕妥珠单抗PIK3CAE545K

、H1047R抗HER2药物耐药预测AKT1E17KCenisertib、Ipatasertib、AfuresertibESR1突变抗雌激素治疗抵抗相关16©2016ThermoFisherScientificCorporation.Allrights

reserved.Oncomine™

Pan-Cancer

Cell-Free

Assay：泛癌种液体活检AssayConfigurationUniqueGenesDNARNAPan

CancerTNA(DNA

+RNA)525012Hotspot

GenesTumorSuppressorGenesCopyNumberGenesFusion/METExonSkippingAKT1ALKARARAFBRAFCHEK2CTNNB1DDR2EGFRERBB2ERBB3ESR1FGFR1FGFR2FGFR3FGFR4FLT3GNA11GNAQGNASHRASIDH1IDH2KITKRASMAP2K1MAP2K2METMTORNRASNTRK1NTRK3PDGFRAPIK3CARAF1RETROS1SF3B1SMAD4SMOAPCFBXW7PTENTP53CCND1CCND2CCND3CDK4CDK6EGFRERBB2FGFR1FGFR2FGFR3METMYCALKBRAFERGETV1FGFR1FGFR2FGFR3METNTRK1NTRK3RETROS1适用多癌种ForResearchUseonly.Notforuseindiagnostic

procedures.©2016ThermoFisherScientificCorporation.Allrights

reserved.ForResearchUseOnly.Notforuseindiagnostic

proceduresBladder（膀胱癌）Brain

and

CNS（脑癌）Breast（乳腺癌）Cervical（颈椎）Colorectal（结直肠癌）Endometrial（子宫内膜癌）Esophageal（食道癌）Gastric（胃癌）Head

and

Neck（头颈癌）Kidney（肾癌）Liver（肝癌）Lung（肺癌）Melanoma（黑色素瘤）Ovarian（卵巢癌）Pancreatic（胰腺癌）Prostate（前列腺癌）Sarcoma（肉瘤） Thyroid（甲状腺癌）

17©2016ThermoFisherScientificCorporation.Allrights

reserved.精心选择的基因列表为更多患者提供精准治疗的可能ApprovedLabelsGuidelinesClinical

TrialsHotspotsBRAFEGFRKRASNRASCNV

ERBB2METFusionsALKROS1Hotspots

BRAFEGFRERBB2KITKRASNRASPDGFRACNV

ERBB2METFusionsALKMETRETROS1AKT1ALKARARAFBRAFCCND1CCND2CCND3CDK4CDK6CHEK2DDR2EGFRERBB2ERBB3ESR1FBXW7FGFR1FGFR2FGFR3FGFR4FLT3GNA11GNAQGNASHRASIDH1IDH2KITKRASMAP2K1MAP2K2METMTORMYCNRASNTRK1NTRK3PDGFRAPIK3CAPTENRAF1RETROS1SMOTP53如何选择靶基因？Oncomine™Pan-CancerCell-Free

AssayForResearchUseonly.Notforuseindiagnostic

procedures.©2016ThermoFisherScientificCorporation.Allrights

reserved.ForResearchUseOnly.Notforuseindiagnostic

procedures18©2016ThermoFisherScientificCorporation.Allrights

reserved.试剂盒效能：使用标准品检测灵敏度和特异性ng

of

input

cfDNAMinimum

coverageHighSensitivityand

Specificity0.1%Limitof

Detection19ForResearchUseOnly.Notforuseindiagnostic

procedures1ngcfDNA–0.6%

LOD5ngcfDNA–0.25%

LOD10ngcfDNA–0.15%

LOD20ngcfDNA–0.1%

LOD30ngcfDNA–0.05%

LODSampleSensitivitySpecificityPan-Cancer0.1%MM80%90%0.5%MM99%99%Lung0.1%

MM92.2%99.7%0.5%

MM>99.9%99.6%Colon0.1%

MM85.9%>99.9%0.5%

MM>99.9%>99.9%Breast0.1%

MM81.3%>99.9%0.5%

MM>99.9%>99.9%效能如何？19©2016ThermoFisherScientificCorporation.Allrights

reserved.20高通量测序方案：按需选择合适的Ion

S5TM芯片Ion540™

Chip60–80M

readsIon530™

Chip15–20M

readsOncomine™LungcfTNA

Assay6-plex24-plexOncomine™BreastcfDNAAssay

v25-plex20-plexOncomine™ColoncfDNA

Assay6-plex24-plexOncomine™Pan-Cancer

Cell-Free

Assay 1-plex 4-plex*The

content

provided

herein

may

relate

to

products

that

have

not

been

officially

released

and

is

subject

to

change

withoutnotice.©2016ThermoFisherScientificCorporation.Allrights

reserved.8-plexIon550™

Chip100–130M

reads需要多大通量的仪器？20©2016ThermoFisherScientificCorporation.Allrights

reserved.21基于Ion

Reporter服务器的数据过滤流程280totalvariantsto

examine8totalfusions

detected2Oncominefusions

detected插件自动过滤数据：

Oncomine

Variant

Annotator

plug-inannotatesandfiltersvariantstofindtherelevant

few©20F1or6RTesheearrcmh

oUsFeiOshnley.rNSotcfioernutsieficinCdiaogrnpoosrtiac

tpiroonce.dAurlelsr.ights

reserved.如何过滤突变信息？21©2016ThermoFisherScientificCorporation.Allrights

reserved.软件配套：提供靶向治疗研究报告，打通最后一公里如何出具报告？基于Oncomine™Knowledgebase给出汉化版靶向用药指导建议22©2016ThermoFisherScientificCorporation.Allrights

reserved.实验室Th成报告Oncomine™KnowledgebaseReporter快速的两日Oncomine™

cfTNA

Assay流程助力临床研究需求模板制备测序cfTNA

分离提取MagMAX™cfTNA

分离提取试剂盒IonS5™andIon

S5™XL

SystemsAlsoenabledonIonPGM™andIonProton™Systems数据分析VariantcallerinTorrentSuite™and

IonReporter™

Softwar