Rhabdomyosarcomas in Aging AJ Mice 英文参考文献.docVIP

RhabdomyosarcomasinAgingA/JMice RogerB.Sher,GregoryA.Cox,KevinD.Mills,JohnP.Sundberg* TheJacksonLaboratory,BarHarbor,Maine,UnitedStatesofAmerica Abstract Rhabdomyosarcomas(RSCs)areskeletalmuscleneoplasmsfoundinhumansanddomesticmammals.TheA/Jinbredstrain developedahighfrequency(between70–80%)ofadultpleomorphictype(APT)RSCat.20monthsofagewhileBALB/cByJ also developRSC but less frequently. Theseneoplasms invaded skeletal muscle surrounding either the axial or proximal appendicularskeletonandwerecharacterizedbypleomorphiccellswithabundanteosinophiliccytoplasm,multiplenuclei, andcrossstriations.Thediagnosiswasconfirmedbydetectionofalpha-sarcomericactinandmyogeninintheneoplastic cells using immunocytochemistry. The A/J strain, but not the related BALB/c substrains, is also characterised by a progressive muscular dystrophy homologous to limb-girdle muscular dystrophy type 2B. The association between the development of RSC in similar muscle groups to those most severely affected by the progressive muscular dystrophy suggestedthattheseneoplasmsdevelopedfromabnormalregenerationoftheskeletalmuscleexacerbatedbythedysferlin mutation. Transcriptome analyses of RSCs revealed marked downregulation of genes in muscular development and function signaling networks. Non-synonymous coding SNPs were found in Myl1, Abra, Sgca, Ttn, and Kcnj12 suggesting thesemaybeimportantinthepathogenesisofRSC.ThesestudiessuggestthatAstrainsofmicecanbeusefulmodelsfor dissectingthemoleculargeneticbasisfordevelopment,progression,andultimatelyfortestingnovelanticancertherapeutic agentsdealingwithrhabdomyosarcoma. Citation:SherRB,CoxGA,MillsKD,SundbergJP(2011)RhabdomyosarcomasinAgingA/JMice.PLoSONE6(8):e23498.doi:10.1371/journal.pone.0023498 Editor:PaulMcNeil,MedicalCollegeofGeorgia,UnitedStatesofAmerica ReceivedJune8,2011;AcceptedJuly19,2011;PublishedAugust10,2011 Copyright:?2011Sheretal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,