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

View/ Open
Author
Craig, Justin M.
Vena, Natalie
Idbaih, Ahmed
Fouse, Shaun D.
Ozek, Memet
Sav, Aydin
Margraf, Linda R.
Eberhart, Charles G.
Norden, Andrew D.
Hill, D. Ashley
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1371/journal.pone.0038881Metadata
Show full item recordCitation
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.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376148/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:10436306
Collections
- HMS Scholarly Articles [17714]
Contact administrator regarding this item (to report mistakes or request changes)