Research Papers:

Targeted or whole genome sequencing of formalin fixed tissue samples: potential applications in cancer genomics

Sarah Munchel, Yen Hoang, Yue Zhao, Joseph Cottrell, Brandy Klotzle, Andrew K. Godwin, Devin Koestler, Peter Beyerlein, Jian-Bing Fan, Marina Bibikova and Jeremy Chien _

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Oncotarget. 2015; 6:25943-25961. https://doi.org/10.18632/oncotarget.4671

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Sarah Munchel1,*, Yen Hoang2,5,*, Yue Zhao1, Joseph Cottrell1, Brandy Klotzle1, Andrew K. Godwin3, Devin Koestler4, Peter Beyerlein2, Jian-Bing Fan1, Marina Bibikova1, Jeremy Chien5

1Illumina, Inc., San Diego, CA, USA

2Department of Bioinformatics and Biosystems Technology, University of Applied Sciences Wildau, Wildau, Germany

3Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA

4Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA

5Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS, USA

*These authors have contributed equally to this work

Correspondence to:

Jeremy Chien, e-mail: [email protected]

Marina Bibikova, e-mail: [email protected]

Jian-Bing Fan, e-mail: [email protected]

Keywords: cancer genomics, FFPE DNA, whole exome sequencing, whole genome sequencing, copy number alterations

Received: May 13, 2015     Accepted: July 20, 2015     Published: July 31, 2015


Current genomic studies are limited by the poor availability of fresh-frozen tissue samples. Although formalin-fixed diagnostic samples are in abundance, they are seldom used in current genomic studies because of the concern of formalin-fixation artifacts. Better characterization of these artifacts will allow the use of archived clinical specimens in translational and clinical research studies. To provide a systematic analysis of formalin-fixation artifacts on Illumina sequencing, we generated 26 DNA sequencing data sets from 13 pairs of matched formalin-fixed paraffin-embedded (FFPE) and fresh-frozen (FF) tissue samples. The results indicate high rate of concordant calls between matched FF/FFPE pairs at reference and variant positions in three commonly used sequencing approaches (whole genome, whole exome, and targeted exon sequencing). Global mismatch rates and C·G > T·A substitutions were comparable between matched FF/FFPE samples, and discordant rates were low (<0.26%) in all samples. Finally, low-pass whole genome sequencing produces similar pattern of copy number alterations between FF/FFPE pairs. The results from our studies suggest the potential use of diagnostic FFPE samples for cancer genomic studies to characterize and catalog variations in cancer genomes.

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