Allele-Specific Amplification in Cancer Revealed by SNP Array Analysis 英文参考文献.docVIP

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Allele-Specific Amplification in Cancer Revealed by SNP Array Analysis 英文参考文献.doc

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Allele-Specific Amplification in Cancer Revealed by SNP Array Analysis 英文参考文献

Allele-SpecificAmplificationinCancer RevealedbySNPArrayAnalysis Thomas LaFramboise1,2,Barbara A.Weir1,2,Xiaojun Zhao1,Rameen Beroukhim1,2,Cheng Li3,David Harrington3, William R.Sellers1,2,4,Matthew Meyerson1,2,5* 1DepartmentofMedicalOncology,Dana-FarberCancerInstitute,Boston,Massachusetts,UnitedStatesofAmerica,2TheBroadInstituteofHarvardandMIT,Cambridge, Massachusetts, United States of America, 3 Departments of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston,Massachusetts,UnitedStatesofAmerica,4DepartmentofMedicine,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica,5Departmentof Pathology,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica Amplification,deletion,andlossofheterozygosityofgenomicDNAarehallmarksofcancer.Inrecentyearsavarietyof studieshaveemergedmeasuringtotalchromosomalcopynumberatincreasingly highresolution. Similarly,loss-of- heterozygosityeventshavebeenfinelymappedusinghigh-throughputgenotypingtechnologies.Wehavedeveloped aprobe-levelallele-specificquantitationprocedurethatextractsbothcopynumberandallelotypeinformationfrom single nucleotide polymorphism (SNP) array data to arrive at allele-specific copy number across the genome. Our approachappliesanexpectation-maximizationalgorithmtoamodelderivedfromanovelclassificationofSNParray probes.Thismethodisthefirsttoourknowledgethatisableto(a)determinethegeneralizedgenotypeofaberrant samplesateachSNPsite(e.g.,CCCCTatanamplifiedsite),and(b)inferthecopynumberofeachparentalchromosome acrossthegenome.Withthismethod,weareabletodeterminenotjustwhereamplificationsanddeletionsoccur,but also the haplotype of the region being amplified or deleted. The merit of our model and general approach is demonstrated by very precise genotyping of normal samples, and our allele-specific copy number inferences are validatedusingPCRexperiments.Applyingourmethodtoacollectionoflungcancersamples,weareabletoconclude that amplification