Proprietary&

Confidential你所需，我所有——腫瘤液體活檢方案有Thermo

Fisher就夠了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多基因檢測為相關指南所推薦精準治療方案的制定離不開多基因檢測，多種相關指南均建議實體腫瘤患者可嘗試多基因檢測。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.實時的腫瘤分子分型有助于選擇最為合適的治療策略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)腫瘤分子分型的時空特異性治療壓力可能會導致腫瘤發Th變異，產Th耐藥突變或者驅動基因的改變3ForResearchUseOnly.Notforuseindiagnostic

procedures3?2016ThermoFisherScientificCorporation.Allrights

reserved.液體活檢可作為組織活檢的有效補充液體活檢非侵入性的實時取樣：為需要實時監控療效的靶向治療患者提供耐藥監測的可能取樣容易：為無手術樣本或難以穿刺的腫瘤患者提供精準靶向治療方案的可能4ForResearchUseOnly.Notforuseindiagnostic

procedures4?2016ThermoFisherScientificCorporation.Allrights

reserved.NCCN

Guideline和CSCO指南的建議中國臨床腫瘤學會（CSCO）原發性肺癌診療指南

2017.V15ForResearchUseOnly.Notforuseindiagnostic

procedures5?2016ThermoFisherScientificCorporation.Allrights

reserved.液體活檢的臨床意義治療方案選擇療效監控復發監控血液樣本、手術樣本及術后三天樣本3

weeks

為周期取樣，持續6-8輪3-6個月為周期取樣Solid

tumorsample中等靈敏度價格適中高靈敏度低價最高靈敏度低價市場需求適用平臺腫瘤患者疾病周期一代測序：組織NGS(0.1%to1%

LOD)：組織

&血液數字PCRNGS(0.1%

LOD)數字PCRNGS(0.1%

LOD)Liquid

biopsysample早期診斷(Screening)Liquid

biopsysample血液樣本高靈敏度低價NGS(large

pan-cancer

panels)*PiperJaffray,The2015LiquidBiopsyReport,September

20156ForResearchUseOnly.Notforuseindiagnostic

procedures6?2016ThermoFisherScientificCorporation.Allrights

reserved.對檢測靈敏度要求高cfDNA中樣本間差異大，早期患者ctDNA的含量低對檢測靈敏度要求高 ctDNA豐度變化大ctDNA突 變比例低檢測目的

不同

需要不同的檢測方案定性

or

定量單基因or多基因檢測結果

解讀需要醫學的解讀需要相應指南規范解讀液體活檢所面臨的挑戰7ForResearchUseOnly.Notforuseindiagnostic

procedures7?2016ThermoFisherScientificCorporation.Allrights

reserved.最接近臨床轉化的NGS液體活檢應用治療方案選擇療效監控復發監控血液樣本、手術樣本及術后三天樣本3

weeks

為周期取樣，持續6-8輪3-6個月為周期取樣Solid

tumorsample中等靈敏度價格適中高靈敏度低價最高靈敏度低價市場需求適用平臺腫瘤患者疾病周期一代測序：組織NGS(0.1%to1%

LOD)：組織

&血液數字PCRNGS(0.1%

LOD)數字PCRNGS(0.1%

LOD)Liquid

biopsysample早期診斷(Screening)Liquid

biopsysample血液樣本高靈敏度低價NGS(large

pan-cancer

panels)*PiperJaffray,The2015LiquidBiopsyReport,September

20158ForResearchUseOnly.Notforuseindiagnostic

procedures8?2016ThermoFisherScientificCorporation.Allrights

reserved.Oncomine?液體活檢試劑盒：一管血實現多基因0.1%低頻突變檢測肺癌LungcfDNA

Assay11

genesHotspots肺癌LungcfTNA

Assay12genesDNAand

RNAHotspotsCNVs,

Fusion泛癌種Pan-cancercfTNA

Assay52genesDNAandRNAHotspots,

CNVsFusions,

TumorSuppressor乳腺癌BreastcfDNAAssay

v212

genesHotspotsCNVsTP53結直腸癌ColoncfDNA

Assay14

genesHotspots乳腺癌BreastcfDNA

Assay10

genesHotspots9ForResearchUseOnly.Notforuseindiagnostic

procedures9?2016ThermoFisherScientificCorporation.Allrights

reserved.晚期驅動基因陽性NSCLC的液體活檢：治療方案選擇及耐藥檢測中國臨床腫瘤學會（CSCO）原發性肺癌診療指南

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

procedures10?2016ThermoFisherScientificCorporation.Allrights

reserved.Oncomine?

lung

cfTNAAssay：NSCLC突變、融合和CNV液體活檢cfDNA&cfRNAIonTorrent?Oncomine?Lung

Cell-FreeTotalNucleicAcidResearch

Assay(單個文庫)ALKBRAFEGFRERBB2KRASMAP2K1METNRASPIK3CARETROS1TP53125811>169GenesAmpliconsGeneswithkeyhotspot

mutationsHotspotSNVsand

indels49Fusions:ALK，RET,

ROS1基因突變類型靶向藥物EGFRExon18-21

突變（敏感&耐藥）吉非替尼、厄洛替尼、?？颂婺?、阿法替尼、達克替尼、奧希替尼ALK融合（敏感）/突變（耐藥）克唑替尼、色瑞替尼、艾樂替尼、Brigatinib、LorlatinibROS1融合（敏感）克唑替尼BRAFV600E（敏感）達拉非尼聯合曲美替尼MET擴增/14外顯子跳躍突變（敏感）克唑替尼、沃利替尼（和記黃埔，臨床階段）ERBB2（HER2）Exon20突變（敏感）阿法替尼RET融合（敏感）卡博替尼、凡德他尼KRAS/NRASG12X,

G13X,

Q61X

（耐藥）不合適用TKISNVLODdownto0.1%with20nginput,samesensitivityand

specificityFusions:ALK，RET,ROS1—at1%

LODCNVMET，METexon14

skipping11?2016ThermoFisherScientificCorporation.Allrights

reserved.IV期結直腸癌治療方案藥物作用機制基因檢測貝伐珠單抗（安維?。┞摵?-氟尿嘧啶（化療）抗血管Th成（VEGF）無西妥昔單抗（愛必妥）/帕尼單抗聯合伊立替康（化療）抑制表皮Th長因子（EGFR）KRAS/NRAS/BRAF（野Th型敏感）帕母單抗/納武單抗抑制PD-1與PD-L1結合（免疫治療）dMMR（DNA錯配修復基因缺陷）MSI-H（微衛星不穩定）晚期結直腸癌的治療方案結直腸癌靶向治療耐藥檢測Prevalenceofgeneticalterationsassociatedwithdenovoresistancetoanti-EGFRtherapiesin

mCRC.結直腸癌96%的靶向治療（西妥昔單抗和帕尼單抗）耐藥發Th與KRAS，NRAS，BRAF，EGFR的突變相關

；EGFR胞外結構域的變體（s492r）提示患者會對西妥昔單抗治療產Th抗性，對帕尼單抗治療則不然；SandraMisaleetal.CancerDiscovery

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

reserved.晚期結直腸癌的靶向治療：CSCO指南2017版13?2016ThermoFisherScientificCorporation.Allrights

reserved.Oncomine?

Colon

cfDNAAssay：結直腸癌液體活檢NCCN推薦檢測的耐藥基因Oncomine?

cfDNA

Colon

Cancer

Assay涵蓋熱點突變治療方案KRASp.A146Tp.Q61Hp.Q61Lp.Q61Rp.G13Dp.G13Cp.G12A

p.G12Dp.G12Fp.G12Vp.G12Cp.G12R

p.G12S野Th型：化療+帕尼單抗/西妥昔單抗（愛必妥）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：化療+帕尼單抗/西妥昔單抗（愛必妥）BRAFp.V600Ep.L597V

p.D594G野Th型：化療+帕尼單抗/西妥昔單抗（愛必妥）PIK3CAp.E542Kp.E545Kp.E545Qp.E545Gp.Q546Kp.Q546P

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

p.G1049R野Th型：化療+帕尼單抗/西妥昔單抗（愛必妥）Panel設計 熱點突變基因（14基因）涵蓋基因KRAS,NRAS,BRAF,

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

TP53,APC14?2016ThermoFisherScientificCorporation.Allrights

reserved.乳腺癌分子亞型病理系統性輔助治療Luminal

（管腔或激素受體陽性）A型ER+和（或）PR+Ki67低表達（<15%）內分泌治療為主

化療Luminal（管腔或激素受體陽性）

B型HER2過表達型ER+和（或）PR+Her2-Ki67高表達（≥15%）內分泌治療±細胞毒治療ER+和（或）PR+Her2+Ki67高表達（≥15%）細胞毒治療+內分泌治療+抗HER2靶向治療ER-

PR-Her+細胞毒治療+抗HER2靶向治療基底樣性ER-

PR-Her2-細胞毒治療BRCA突變患者：PARP抑制劑，如奧拉帕尼不同分子亞型乳腺癌的輔助治療方案選擇15?2016ThermoFisherScientificCorporation.Allrights

reserved.Oncomine?

Breast

cfDNA

Assay：乳腺癌突變和CNV液體活檢cfDNAIonTorrent?Oncomine?BreastcfDNAResearchAssayv2(單管檢測)AKT1CCND1EGFRERBB2ERBB3ESR1FBXW7FGFR1KRASPIK3CASF3B1TP53127610>152GenesAmpliconsGeneswithkeyhotspotmutationsHotspotSNVsand

indelsSNVLODdownto0.1%with20nginputsamesensitivityand

specificityCNVsCCND1,ERBB2,FGFR1detectfoldchangeof

1.2–1.4xTP53Morecompletecoverage;0.5%LODondenovo

sequencing基因突變類型靶向藥物ERBB2（HER2）擴增曲妥珠單抗（赫賽?。?、拉帕替尼、帕妥珠單抗PIK3CAE545K

、H1047R抗HER2藥物耐藥預測AKT1E17KCenisertib、Ipatasertib、AfuresertibESR1突變抗雌激素治療抵抗相關16?2016ThermoFisherScientificCorporation.Allrights

reserved.Oncomine?

Pan-Cancer

Cell-Free

Assay：泛癌種液體活檢AssayConfigurationUniqueGenesDNARNAPan

CancerTNA(DNA

+RNA)525012Hotspot

GenesTumorSuppressorGenesCopyNumberGenesFusion/METExonSkippingAKT1ALKARARAFBRAFCHEK2CTNNB1DDR2EGFRERBB2ERBB3ESR1FGFR1FGFR2FGFR3FGFR4FLT3GNA11GNAQGNASHRASIDH1IDH2KITKRASMAP2K1MAP2K2METMTORNRASNTRK1NTRK3PDGFRAPIK3CARAF1RETROS1SF3B1SMAD4SMOAPCFBXW7PTENTP53CCND1CCND2CCND3CDK4CDK6EGFRERBB2FGFR1FGFR2FGFR3METMYCALKBRAFERGETV1FGFR1FGFR2FGFR3METNTRK1NTRK3RETROS1適用多癌種ForResearchUseonly.Notforuseindiagnostic

procedures.?2016ThermoFisherScientificCorporation.Allrights

reserved.ForResearchUseOnly.Notforuseindiagnostic

proceduresBladder（膀胱癌）Brain

and

CNS（腦癌）Breast（乳腺癌）Cervical（頸椎）Colorectal（結直腸癌）Endometrial（子宮內膜癌）Esophageal（食道癌）Gastric（胃癌）Head

and

Neck（頭頸癌）Kidney（腎癌）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（甲狀腺癌）

17?2016ThermoFisherScientificCorporation.Allrights

reserved.精心選擇的基因列表為更多患者提供精準治療的可能ApprovedLabelsGuidelinesClinical

TrialsHotspotsBRAFEGFRKRASNRASCNV

ERBB2METFusionsALKROS1Hotspots

BRAFEGFRERBB2KITKRASNRASPDGFRACNV

ERBB2METFusionsALKMETRETROS1AKT1ALKARARAFBRAFCCND1CCND2CCND3CDK4CDK6CHEK2DDR2EGFRERBB2ERBB3ESR1FBXW7FGFR1FGFR2FGFR3FGFR4FLT3GNA11GNAQGNASHRASIDH1IDH2KITKRASMAP2K1MAP2K2METMTORMYCNRASNTRK1NTRK3PDGFRAPIK3CAPTENRAF1RETROS1SMOTP53如何選擇靶基因？Oncomine?Pan-CancerCell-Free

AssayForResearchUseonly.Notforuseindiagnostic

procedures.?2016ThermoFisherScientificCorporation.Allrights

reserved.ForResearchUseOnly.Notforuseindiagnostic

procedures18?2016ThermoFisherScientificCorporation.Allrights

reserved.試劑盒效能：使用標準品檢測靈敏度和特異性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高通量測序方案：按需選擇合適的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需要多大通量的儀器？20?2016ThermoFisherScientificCorporation.Allrights

reserved.21基于Ion

Reporter服務器的數據過濾流程280totalvariantsto

examine8totalfusions

detected2Oncominefusions

detected插件自動過濾數據：

Oncomine

Variant

Annotator

plug-inannotatesandfiltersvariantstofindtherelevant

few?20F1or6RTesheearrcmh

oUsFeiOshnley.rNSotcfioernutsieficinCdiaogrnpoosrtiac

tpiroonce.dAurlelsr.ights

reserved.如何過濾突變信息？21?2016ThermoFisherScientificCorporation.Allrights

reserved.軟件配套：提供靶向治療研究報告，打通最后一公里如何出具報告？基于Oncomine?Knowledgebase給出漢化版靶向用藥指導建議22?2016ThermoFisherScientificCorporation.Allrights

reserved.實驗室Th成報告Oncomine?KnowledgebaseReporter快速的兩日Oncomine?

cfTNA

Assay流程助力臨床研究需求模板制備測序cfTNA

分離提取MagMAX?cfTNA

分離提取試劑盒IonS5?andIon

S5?XL

SystemsAlsoenabledonIonPGM?andIonProton?Systems數據分析VariantcallerinTorrentSuite?and

IonReporter?

Softwar