DNA Fragmentation Simulation Method (FSM) and Fragment Size Matching Improve aCGH Performance of FFPE Tissues

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DNA Fragmentation Simulation Method (FSM) and Fragment Size Matching Improve aCGH Performance of FFPE Tissues

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dc.contributor.author Craig, Justin M.
dc.contributor.author Vena, Natalie
dc.contributor.author Idbaih, Ahmed
dc.contributor.author Fouse, Shaun D.
dc.contributor.author Ozek, Memet
dc.contributor.author Sav, Aydin
dc.contributor.author Margraf, Linda R.
dc.contributor.author Eberhart, Charles G.
dc.contributor.author Norden, Andrew D.
dc.contributor.author Ramkissoon, Shakti
dc.contributor.author Hill, D. Ashley
dc.contributor.author Kieran, Mark W.
dc.contributor.author Wen, Patrick Yung Chih
dc.contributor.author Loda, Massimo
dc.contributor.author Santagata, Sandro
dc.contributor.author Ligon, Keith Lloyd
dc.contributor.author Ligon, Azra Hadi
dc.date.accessioned 2013-03-18T19:06:31Z
dc.date.issued 2012
dc.identifier.citation Craig, 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.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:10436306
dc.description.abstract Whole-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.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0038881 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376148/pdf/ en_US
dash.license LAA
dc.subject Biology en_US
dc.subject Computational Biology en_US
dc.subject Genomics en_US
dc.subject Genome Analysis Tools en_US
dc.subject Medicine en_US
dc.subject Clinical Genetics en_US
dc.subject Genetic Testing en_US
dc.subject Diagnostic Medicine en_US
dc.subject Pathology en_US
dc.subject Anatomical Pathology en_US
dc.subject Neuropathology en_US
dc.subject Test Evaluation en_US
dc.subject Oncology en_US
dc.subject Cancer Detection and Diagnosis en_US
dc.subject Cancers and Neoplasms en_US
dc.title DNA Fragmentation Simulation Method (FSM) and Fragment Size Matching Improve aCGH Performance of FFPE Tissues en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Kieran, Mark W.
dc.date.available 2013-03-18T19:06:31Z

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