Pancreatic Cancer Mutation PCR Array

TheHumanPancreaticCancerqBioMarkerSomaticMutationPCRArrayisatranslationalresearchtoolthatallowsrapid,accurate,andcomprehensiveprofilingofthesomaticmutationsinhumanpancreaticcancersamplesinthefollowingkeygenes:APC,BRAF,CDKN2A,CTNNB1,KRAS,NRAS,PIK3CA,SMAD4,andP53.Thesemutationswarrantextensiveinvestigationtoenhancetheunderstandingofcarcinogenesisandidentifypotentialdrugtargets.Numerousresearchstudieshavedemonstratedtheutilityofindividualandmultiplesomaticmutationstatusinformationinidentifyingkeysignalingtransductiondisruptions.Forexample,themutationstatusoftheEGFRandKRASgenescanpredictthephysiologicalresponsetocertaindrugstargetingthesemolecules.TheHumanPancreaticCancerqBiomarkerSomaticMutationPCRArray,withitscomprehensivecontentcoverage,isdesignedforstudyingmutationsinthecontextofpancreaticcancerandhasthepotentialfordiscoveryanddevelopmentofeffectivebiomarkersforthiscancertypeandothercancertypesinwhichthesemutationswereidentified.Thisarrayincludes38DNAsequencemutationassaysdesignedtodetectthemostfrequent,functionallyverified,andbiologicallysignificantmutationsinhumanpancreaticcancer.Thesemutationswerechosenfromcurated,comprehensivesomaticmutationdatabasesandpeer-reviewedscientificliterature,andrepresentthemostfrequentlyrecurringsomaticmutationscompiledfromover3800pancreaticcancersamples.Each96-wellarrayallowsprofilingmutationstatusof2samples,whileeach384-wellformatarrayallowsmutationprofilingof8samples.Thesimplicityoftheproductformatandoperatingprocedureenablesroutinesomaticmutationprofilinginanyresearchlaboratorywithaccesstoreal-timePCRinstruments.

APC:1Assay
ThemostcommonlydetectedAPCinactivationmutationsaremainlycomposedoftruncationmutations(duetononsensemutationsandframeshiftmutations)andpointmutationsbetweencodons1250and1578.

BRAF:1Assay
ThemostimportantBRAFmutationinpancreaticcancerleadstoincreasedkinaseactivity,thep.V600Emutation.

CDKN2A:3Assays
ThetopCDKN2Aloss-of-functionmutationsoccurintheconsensusankyrindomain,whichleadstoinabilitytoformstablecomplexeswithitstargets.

CTNNB1:9Assays
ThemostfrequentlydetectedCTNNB1/beta-cateninmutationsresultinabnormalsignalingintheWNTsignalingpathway.Themutatedcodonsaremainlyseveralserine/threonineresiduestargetedforphosphorylationbyGSK-3beta.

KRAS:10Assays
ThemutationassaysincludethemostfrequentlyoccurringmutationsinKRAScodons12,13,and61.MutationsatthesepositionsresultinreducedintrinsicGTPaseactivityand/orcauseKRAStobecomeunresponsivetoRasGAP.

NRAS:2Assays
ThemostimportantNRASmutationsinpancreaticcanceroccuratcodon61.

PIK3CA:3Assays
ThemostfrequentlyoccurringPIK3CAmutationsmainlybelongtotwoclasses:gain-of-functionkinasedomainactivatingmutationsandhelicaldomainmutationsthatmimicactivationbygrowthfactors.

SMAD4:1Assay
SMAD4encodesamemberoftheSmadfamilyofsignaltransductionproteins.Mutationsordeletionsinthisgenehavebeenshowntoresultinpancreaticcancer,juvenilepolyposissyndrome,andhereditaryhemorrhagictelangiectasiasyndrome.

TP53:8Assays
ThemostfrequentlydetectedsomaticmutationsinTP53arelargelycomposedofDNA-bindingdomainmutationswhichdisrupteitherDNAbindingorproteinstructure.

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Pancreatic Cancer Mutation PCR Array