你所需,我所有-腫瘤液體活檢方案有Thermo Fisher就夠%

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(cè)為相關(guān)指南所推薦精準(zhǔn)治療方案的制定離不開(kāi)多基因檢測(cè)，多種相關(guān)指南均建議實(shí)體腫瘤患者可嘗試多基因檢測(cè)。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(shí)時(shí)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(shí)空特異性治療壓力可能會(huì)導(dǎo)致腫瘤發(fā)Th變異，產(chǎn)Th耐藥突變或者驅(qū)動(dòng)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(bǔ)充液體活檢非侵入性的實(shí)時(shí)取樣：為需要實(shí)時(shí)監(jiān)控療效的靶向治療患者提供耐藥監(jiān)測(cè)的可能取樣容易：為無(wú)手術(shù)樣本或難以穿刺的腫瘤患者提供精準(zhǔn)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(guó)臨床腫瘤學(xué)會(huì)（CSCO）原發(fā)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(jiān)控復(fù)發(fā)監(jiān)控血液樣本、手術(shù)樣本及術(shù)后三天樣本3

weeks

為周期取樣，持續(xù)6-8輪3-6個(gè)月為周期取樣Solid

tumorsample中等靈敏度價(jià)格適中高靈敏度低價(jià)最高靈敏度低價(jià)市場(chǎng)需求適用平臺(tái)腫瘤患者疾病周期一代測(cè)序：組織NGS(0.1%to1%

LOD)：組織

&血液數(shù)字PCRNGS(0.1%

LOD)數(shù)字PCRNGS(0.1%

LOD)Liquid

biopsysample早期診斷(Screening)Liquid

biopsysample血液樣本高靈敏度低價(jià)NGS(large

pan-cancer

panels)*PiperJaffray,The2015LiquidBiopsyReport,September

20156ForResearchUseOnly.Notforuseindiagnostic

procedures6?2016ThermoFisherScientificCorporation.Allrights

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

不同

需要不同的檢測(cè)方案定性

or

定量單基因or多基因檢測(cè)結(jié)果

解讀需要醫(yī)學(xué)的解讀需要相應(yīng)指南規(guī)范解讀液體活檢所面臨的挑戰(zhàn)7ForResearchUseOnly.Notforuseindiagnostic

procedures7?2016ThermoFisherScientificCorporation.Allrights

reserved.最接近臨床轉(zhuǎn)化的NGS液體活檢應(yīng)用治療方案選擇療效監(jiān)控復(fù)發(fā)監(jiān)控血液樣本、手術(shù)樣本及術(shù)后三天樣本3

weeks

為周期取樣，持續(xù)6-8輪3-6個(gè)月為周期取樣Solid

tumorsample中等靈敏度價(jià)格適中高靈敏度低價(jià)最高靈敏度低價(jià)市場(chǎng)需求適用平臺(tái)腫瘤患者疾病周期一代測(cè)序：組織NGS(0.1%to1%

LOD)：組織

&血液數(shù)字PCRNGS(0.1%

LOD)數(shù)字PCRNGS(0.1%

LOD)Liquid

biopsysample早期診斷(Screening)Liquid

biopsysample血液樣本高靈敏度低價(jià)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(shí)現(xiàn)多基因0.1%低頻突變檢測(cè)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(jié)直腸癌ColoncfDNA

Assay14

genesHotspots乳腺癌BreastcfDNA

Assay10

genesHotspots9ForResearchUseOnly.Notforuseindiagnostic

procedures9?2016ThermoFisherScientificCorporation.Allrights

reserved.晚期驅(qū)動(dòng)基因陽(yáng)性NSCLC的液體活檢：治療方案選擇及耐藥檢測(cè)中國(guó)臨床腫瘤學(xué)會(huì)（CSCO）原發(fā)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(gè)文庫(kù))ALKBRAFEGFRERBB2KRASMAP2K1METNRASPIK3CARETROS1TP53125811>169GenesAmpliconsGeneswithkeyhotspot

mutationsHotspotSNVsand

indels49Fusions:ALK，RET,

ROS1基因突變類(lèi)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(dá)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(lè)替尼、Brigatinib、LorlatinibROS1融合（敏感）克唑替尼BRAFV600E（敏感）達(dá)拉非尼聯(lián)合曲美替尼MET擴(kuò)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(jié)直腸癌治療方案藥物作用機(jī)制基因檢測(cè)貝伐珠單抗（安維?。┞?lián)合5-氟尿嘧啶（化療）抗血管Th成（VEGF）無(wú)西妥昔單抗（愛(ài)必妥）/帕尼單抗聯(lián)合伊立替康（化療）抑制表皮Th長(zhǎng)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(jié)合（免疫治療）dMMR（DNA錯(cuò)配修復(fù)基因缺陷）MSI-H（微衛(wèi)星不穩(wěn)定）晚期結(jié)直腸癌的治療方案結(jié)直腸癌靶向治療耐藥檢測(cè)Prevalenceofgeneticalterationsassociatedwithdenovoresistancetoanti-EGFRtherapiesin

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

；EGFR胞外結(jié)構(gòu)域的變體（s492r）提示患者會(huì)對(duì)西妥昔單抗治療產(chǎn)Th抗性，對(duì)帕尼單抗治療則不然；SandraMisaleetal.CancerDiscovery

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

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

reserved.Oncomine?

Colon

cfDNAAssay：結(jié)直腸癌液體活檢NCCN推薦檢測(cè)的耐藥基因Oncomine?

cfDNA

Colon

Cancer

Assay涵蓋熱點(diǎn)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(ài)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(ài)必妥）BRAFp.V600Ep.L597V

p.D594G野Th型：化療+帕尼單抗/西妥昔單抗（愛(ài)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(ài)必妥）Panel設(shè)計(jì) 熱點(diǎn)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(tǒng)性輔助治療Luminal

（管腔或激素受體陽(yáng)性）A型ER+和（或）PR+Ki67低表達(dá)（<15%）內(nèi)分泌治療為主

化療Luminal（管腔或激素受體陽(yáng)性）

B型HER2過(guò)表達(dá)型ER+和（或）PR+Her2-Ki67高表達(dá)（≥15%）內(nèi)分泌治療±細(xì)胞毒治療ER+和（或）PR+Her2+Ki67高表達(dá)（≥15%）細(xì)胞毒治療+內(nèi)分泌治療+抗HER2靶向治療ER-

PR-Her+細(xì)胞毒治療+抗HER2靶向治療基底樣性ER-

PR-Her2-細(xì)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(cè))AKT1CCND1EGFRERBB2ERBB3ESR1FBXW7FGFR1KRASPIK3CASF3B1TP53127610>152GenesAmpliconsGeneswithkeyhotspotmutationsHotspotSNVsand

indelsSNVLODdownto0.1%with20nginputsamesensitivityand

specificityCNVsCCND1,ERBB2,FGFR1detectfoldchangeof

1.2–1.4xTP53Morecompletecoverage;0.5%LODondenovo

sequencing基因突變類(lèi)型靶向藥物ERBB2（HER2）擴(kuò)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(yù)測(cè)AKT1E17KCenisertib、Ipatasertib、AfuresertibESR1突變抗雌激素治療抵抗相關(guān)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(jié)直腸癌）Endometrial（子宮內(nèi)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(zhǔn)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(biāo)準(zhǔn)品檢測(cè)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(cè)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(wù)器的數(shù)據(jù)過(guò)濾流程280totalvariantsto

examine8totalfusions

detected2Oncominefusions

detected插件自動(dòng)過(guò)濾數(shù)據(jù)：

Oncomine

Variant

Annotator

plug-inannotatesandfiltersvariantstofindtherelevant

few?20F1or6RTesheearrcmh

oUsFeiOshnley.rNSotcfioernutsieficinCdiaogrnpoosrtiac

tpiroonce.dAurlelsr.ights

reserved.如何過(guò)濾突變信息？21?2016ThermoFisherScientificCorporation.Allrights

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

reserved.實(shí)驗(yàn)室Th成報(bào)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(cè)序cfTNA

分離提取MagMAX?cfTNA

分離提取試劑盒IonS5?andIon

S5?XL

SystemsAlsoenabledonIonPGM?andIonProton?Systems數(shù)據(jù)分析VariantcallerinTorrentSuite?and

IonReporter?

Softwar