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Robustness of Next Generation Sequencing on Older Formalin-Fixed Paraffin-Embedded Tissue
Journal article   Open access   Peer reviewed

Robustness of Next Generation Sequencing on Older Formalin-Fixed Paraffin-Embedded Tissue

Danielle Mercatante Carrick, Michele G Mehaffey, Michael C Sachs, Sean Altekruse, Corinne Camalier, Rodrigo Chuaqui, Wendy Cozen, Biswajit Das, Brenda Y Hernandez, Chih-Jian Lih, …
PloS one, Vol.10(7), pp.e0127353-e0127353
2015
DOI: 10.1371/journal.pone.0127353
PMCID: PMC4519244
PMID: 26222067
url
https://doi.org/10.1371/journal.pone.0127353View
Published (Version of record) Open Access

Abstract

Next Generation Sequencing (NGS) technologies are used to detect somatic mutations in tumors and study germ line variation. Most NGS studies use DNA isolated from whole blood or fresh frozen tissue. However, formalin-fixed paraffin-embedded (FFPE) tissues are one of the most widely available clinical specimens. Their potential utility as a source of DNA for NGS would greatly enhance population-based cancer studies. While preliminary studies suggest FFPE tissue may be used for NGS, the feasibility of using archived FFPE specimens in population based studies and the effect of storage time on these specimens needs to be determined. We conducted a study to determine whether DNA in archived FFPE high-grade ovarian serous adenocarcinomas from Surveillance, Epidemiology and End Results (SEER) registries Residual Tissue Repositories (RTR) was present in sufficient quantity and quality for NGS assays. Fifty-nine FFPE tissues, stored from 3 to 32 years, were obtained from three SEER RTR sites. DNA was extracted, quantified, quality assessed, and subjected to whole exome sequencing (WES). Following DNA extraction, 58 of 59 specimens (98%) yielded DNA and moved on to the library generation step followed by WES. Specimens stored for longer periods of time had significantly lower coverage of the target region (6% lower per 10 years, 95% CI: 3-10%) and lower average read depth (40x lower per 10 years, 95% CI: 18-60), although sufficient quality and quantity of WES data was obtained for data mining. Overall, 90% (53/59) of specimens provided usable NGS data regardless of storage time. This feasibility study demonstrates FFPE specimens acquired from SEER registries after varying lengths of storage time and under varying storage conditions are a promising source of DNA for NGS.
SEER Program Adenocarcinoma - pathology Formaldehyde - chemistry Humans Ovarian Neoplasms - pathology DNA, Neoplasm - chemistry Ovarian Neoplasms - genetics Paraffin Embedding Specimen Handling Female Adenocarcinoma - genetics DNA, Neoplasm - genetics Tissue Fixation High-Throughput Nucleotide Sequencing - methods

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