Quantification of Normal Cell Fraction and Copy Number Neutral LOH in Clinical Lung Cancer Samples Using SNP Array Data 英文参考文献.docVIP

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Quantification of Normal Cell Fraction and Copy Number Neutral LOH in Clinical Lung Cancer Samples Using SNP Array Data 英文参考文献.doc

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Quantification of Normal Cell Fraction and Copy Number Neutral LOH in Clinical Lung Cancer Samples Using SNP Array Data 英文参考文献

QuantificationofNormalCellFractionandCopyNumber NeutralLOHinClinicalLungCancerSamplesUsingSNP ArrayData HannaGo¨ransson1,KarolinaEdlund2,MariaRyda?ker1,MarkusRasmussen1,JohanWinquist1 ,Simon Ekman3,MichaelBergqvist3,AndrewThomas4,MatsLambe5,6,RichardRosenquist2,LarsHolmberg6,7,8, PatrickMicke2,JohanBotling2,AndersIsaksson1* 1DepartmentofMedicalSciences,UppsalaUniversity,Uppsala,Sweden,2DepartmentofGeneticsandPathology,UppsalaUniversity,Uppsala,Sweden,3Departmentof Oncology, Uppsala University Hospital, Uppsala, Sweden, 4AstraZeneca, Alderley Park, Macclesfield, United Kingdom, 5Department of Medical Epidemiology and Biostatistics,KarolinskaInstitute,Stockholm,Sweden,6RegionalOncologicCentre,UppsalaUniversityHospital,Uppsala,Sweden,7DivisionofCancerStudies,Medical School,King’sCollegeLondon,London,UnitedKingdom,8DepartmentofSurgicalSciences,UppsalaUniversity,Uppsala,Sweden Abstract Background: Technologies based on DNA microarrays have the potential to provide detailed information on genomic aberrations in tumor cells. In practice a major obstacle for quantitative detection of aberrations is the heterogeneity of clinicaltumortissue.Sincetumortissueinvariably containsgeneticallynormalstromalcells,thismayleadtoafailureto detectaberrationsinthetumorcells. PrincipalFinding:UsingSNParraydatafrom44non-smallcelllungcancersampleswehavedevelopedabioinformatic algorithm that accurately models the fractions of normal and tumor cells in clinical tumor samples. The proportion of normal cells in combination with SNP array data can be used to detect and quantify copy number neutral loss-of- heterozygosity(CNNLOH)inthetumorcellsbothincrudetumortissueandinsamplesenrichedfortumorcellsbylaser capturemicrodissection. Conclusion: Genome-wide quantitative analysis of CNNLOH using the CNNLOH Quantifier method can help to identify recurrentaberrationscontributingtotumordevelopmentinclinicaltumorsamples.Inaddition,SNP-arraybasedanalysisof CNNLOHmaybecomeimportantfordetectionofaberration