Show simple item record

dc.contributor.authorCraig, Justin M.
dc.contributor.authorVena, Natalie
dc.contributor.authorIdbaih, Ahmed
dc.contributor.authorFouse, Shaun D.
dc.contributor.authorOzek, Memet
dc.contributor.authorSav, Aydin
dc.contributor.authorMargraf, Linda R.
dc.contributor.authorEberhart, Charles G.
dc.contributor.authorNorden, Andrew D.
dc.contributor.authorRamkissoon, Shakti
dc.contributor.authorHill, D. Ashley
dc.contributor.authorKieran, Mark W.
dc.contributor.authorWen, Patrick Yung Chih
dc.contributor.authorLoda, Massimo
dc.contributor.authorSantagata, Sandro
dc.contributor.authorLigon, Keith Lloyd
dc.contributor.authorLigon, Azra Hadi
dc.date.accessioned2013-03-18T19:06:31Z
dc.date.issued2012
dc.identifier.citationCraig, Justin M., Natalie Vena, Shakti Ramkissoon, Ahmed Idbaih, Shaun D. Fouse, Memet Ozek, Aydin Sav, D. Ashley Hill, Linda R. Margraf, Charles G. Eberhart, Mark W. Kieran, Andrew D. Norden, Patrick Y. Wen, Massimo Loda, Sandro Santagata, Keith L. Ligon, and Azra H. Ligon. 2012. DNA fragmentation simulation method (FSM) and fragment size matching improve aCGH performance of FFPE tissues. PLoS ONE 7(6): e38881.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10436306
dc.description.abstractWhole-genome copy number analysis platforms, such as array comparative genomic hybridization (aCGH) and single nucleotide polymorphism (SNP) arrays, are transformative research discovery tools. In cancer, the identification of genomic aberrations with these approaches has generated important diagnostic and prognostic markers, and critical therapeutic targets. While robust for basic research studies, reliable whole-genome copy number analysis has been unsuccessful in routine clinical practice due to a number of technical limitations. Most important, aCGH results have been suboptimal because of the poor integrity of DNA derived from formalin-fixed paraffin-embedded (FFPE) tissues. Using self-hybridizations of a single DNA sample we observed that aCGH performance is significantly improved by accurate DNA size determination and the matching of test and reference DNA samples so that both possess similar fragment sizes. Based on this observation, we developed a novel DNA fragmentation simulation method (FSM) that allows customized tailoring of the fragment sizes of test and reference samples, thereby lowering array failure rates. To validate our methods, we combined FSM with Universal Linkage System (ULS) labeling to study a cohort of 200 tumor samples using Agilent 1 M feature arrays. Results from FFPE samples were equivalent to results from fresh samples and those available through the glioblastoma Cancer Genome Atlas (TCGA). This study demonstrates that rigorous control of DNA fragment size improves aCGH performance. This methodological advance will permit the routine analysis of FFPE tumor samples for clinical trials and in daily clinical practice.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0038881en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376148/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectComputational Biologyen_US
dc.subjectGenomicsen_US
dc.subjectGenome Analysis Toolsen_US
dc.subjectMedicineen_US
dc.subjectClinical Geneticsen_US
dc.subjectGenetic Testingen_US
dc.subjectDiagnostic Medicineen_US
dc.subjectPathologyen_US
dc.subjectAnatomical Pathologyen_US
dc.subjectNeuropathologyen_US
dc.subjectTest Evaluationen_US
dc.subjectOncologyen_US
dc.subjectCancer Detection and Diagnosisen_US
dc.subjectCancers and Neoplasmsen_US
dc.titleDNA Fragmentation Simulation Method (FSM) and Fragment Size Matching Improve aCGH Performance of FFPE Tissuesen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorKieran, Mark W.
dc.date.available2013-03-18T19:06:31Z
dc.identifier.doi10.1371/journal.pone.0038881*
dash.authorsorderedfalse
dash.contributor.affiliatedRamkissoon, Shakti H.
dash.contributor.affiliatedLigon, Azra
dash.contributor.affiliatedSantagata, Sandro
dash.contributor.affiliatedKieran, Mark W.
dash.contributor.affiliatedLoda, Massimo
dash.contributor.affiliatedLigon, Keith
dash.contributor.affiliatedWen, Patrick


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record