Assessment of concordance between fresh-frozen and formalin-fixed paraffin embedded tumor DNA methylation using a targeted sequencing approach
DNA methylation is altered in many types of disease, including metastatic colorectal cancer. However, the methylome has not yet been fully described in archival formalin-fixed paraffin embedded (FFPE) samples in the context of matched fresh-frozen (FF) tumor material at base-pair resolution using a...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
May 30, 2017
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| In: |
OncoTarget
Year: 2017, Volume: 8, Issue: 29, Pages: 48126-48137 |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.18296 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.18632/oncotarget.18296 Verlag, kostenfrei, Volltext: http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=18296&path[]=58670 
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| Author Notes: | Bruce Moran, Sudipto Das, Dominiek Smeets, Gillian Peutman, Rut Klinger, Bozena Fender, Kate Connor, Matthias Ebert, Timo Gaiser, Jochen H.M. Prehn, Orna Bacon, Elaine Kay, Bryan Hennessy, Verena Murphy, Bauke Ylstra, Diether Lambrechts, Annette T. Byrne, William M. Gallagher and Darran P. O’Connor |
| Summary: | DNA methylation is altered in many types of disease, including metastatic colorectal cancer. However, the methylome has not yet been fully described in archival formalin-fixed paraffin embedded (FFPE) samples in the context of matched fresh-frozen (FF) tumor material at base-pair resolution using a targeted approach. Using next-generation sequencing, we investigated three pairs of matched FFPE and FF samples to determine the extent of their similarity. We identified a ‘bowing’ pattern specific to FFPE samples categorized by a lower CG proportion at the start of sequence reads. We have found no evidence that this affected methylation calling, nor concordance of results. We also found no significant increase in deamination, measured by C>T transitions, previously considered a result of crosslinking DNA by formalin fixation and a barrier to the use of FFPE in methylation studies. The methods used in this study have shown sensitivity of between 60-70% based on positions also methylated in colorectal cancer cell lines. We demonstrate that FFPE material is a useful source of tumor material for methylation studies using targeted sequencing. |
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| Item Description: | Gesehen am 11.06.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.18296 |