ALKBreakApartFISHProbe
AnaplasticlymphomakinasegenecodesfortheALKprotein,atyrosinekinasereceptor.Theseproteinsplayacrucialroleinintracellularsignaltransduction,allowingforcellgrowthanddifferentiation4.
AberrationsintheALKgene,includingoverexpression,deletionandmostcommonlytranslocation,havebeenfoundtoplayasignificantroleinthedevelopmentofover20differenttypesofcancers,especiallylungandlymph1.Astranslocationsmakeupalmost75%ofallgeneticabnormalitiesexhibitedincancercells,trackingALK’sintraandinterchromosomalmigrationcanbeusefulindiagnosisandtreatment3.
TheidentityofthegenethatALKfuseswithduringtranslocationisalsocriticalindeterminingtreatment,asdifferentfusionpartnershavebeenshowntoresponddifferentiallytochemodrugs2.AlthoughEML4remainsALK’smostprevalent,well-studiedfusionpartner,othergeneshavealsodemonstratedoncogeniceffectswhenconjoinedwithALK2,5.Infact,over30differentfusiongeneshavebeenidentified,albeitinlowerfrequenciesthanEML4,intumorsofALKassociatedcancers2.Thetypeandprevalenceofthesefusionproteinsarespecifictothetypeofcancerunderstudy,furtherproofofALK’sutilityindiagnosis1,2.
OurbreakapartprobescaneffectivelymapALKshuffling,whileourfusionprobescantestforthepresenceofspecificfusionproteinsifyoualreadyhaveatargetgeneinmind.
1.Shackelford,R.E.,Vora,M.,Mayhall,K.,&Cotelingam,J.(2014).ALK-rearrangementsandtestingmethodsinnon-smallcelllungcancer:areview.Genes&cancer,5(1-2),1-14.
2.Childress,M.A.,Himmelberg,S.M.,Chen,H.,Deng,W.,Davies,M.A.,&Lovly,C.M.(2018).ALKfusionpartnersimpactresponsetoALKinhibition:differentialeffectsonsensitivity,cellularphenotypes,andbiochemicalproperties.MolecularCancerResearch,16(11),1724-1736.
3.Futreal,P.A.,Coin,L.,Marshall,M.,Down,T.,Hubbard,T.,Wooster,R.,...&Stratton,M.R.(2004).Acensusofhumancancergenes.Naturereviewscancer,4(3),177.
4.https://ghr.nlm.nih.gov/gene/ALK
5.SABIr,S.,Yeoh,S.,Jackson,G.,&Bayliss,R.(2017).EML4-ALKvariants:BIOLOGicalandmolecularproperties,andtheimplicationsforpatients.Cancers,9(9),118.
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