Why Formalin-fixed, Paraffin-embedded Biospecimens Must Be Used in Genomic Medicine: An Evidence-based Review and Conclusion

William Mathieson, Geraldine A. Thomas

Journal of Histochemistry & Cytochemistry, July 2020, 1–10

https://doi.org/10.1369/0022155420945050

Abstract

Fresh-frozen tissue is the “gold standard” biospecimen type for next-generation sequencing (NGS). However, collecting
frozen tissue is usually not feasible because clinical workflows deliver formalin-fixed, paraffin-embedded (FFPE) tissue blocks.
Some clinicians and researchers are reticent to embrace the use of FFPE tissue for NGS because FFPE tissue can yield low
quantities of degraded DNA, containing formalin-induced mutations. We describe the process by which formalin-induced
deamination can lead to artifactual cytosine (C) to thymine (T) and guanine (G) to adenine (A) (C:G > T:A) mutation calls
and perform a literature review of 17 publications that compare NGS data from patient-matched fresh-frozen and FFPE
tissue blocks. We conclude that although it is indeed true that sequencing data from FFPE tissue can be poorer than those
from frozen tissue, any differences occur at an inconsequential magnitude, and FFPE biospecimens can be used in genomic
medicine with confidence.

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