2021
DOI: 10.1101/2021.03.11.434918
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The mutational signatures of formalin fixation on the human genome

Abstract: Background: Formalin fixation and paraffin embedding (FFPE) of patient material remains standard practice in clinical pathology labs around the world. Clinical archives of patient material near-exclusively consist of FFPE blocks. The ability to perform high quality genome sequencing on FFPE-derived DNA would accelerate a broad spectrum of medical research. However, formalin is a recognised mutagen and sequencing of DNA derived from FFPE material is known to be riddled with artefactual mutations. Results: Here … Show more

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Cited by 7 publications
(5 citation statements)
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“…The mutational signature of IMFT was characterized by predominant C>T transitions, as seen in most solid tumors (40). Additionally, cytosine deamination in formalin-fixed, paraffinembedded (FFPE) material is known to induce an artefact of C>T transitions with a signature highly similar to SBS30 (41). However, the clock-like signatures of SBS5 and SBS1 observed in our IMFT cohort suggest the etiology linked with ageing and allow us to disregard the artefactual contribution from FFPE material in this study.…”
Section: Discussionmentioning
confidence: 83%
“…The mutational signature of IMFT was characterized by predominant C>T transitions, as seen in most solid tumors (40). Additionally, cytosine deamination in formalin-fixed, paraffinembedded (FFPE) material is known to induce an artefact of C>T transitions with a signature highly similar to SBS30 (41). However, the clock-like signatures of SBS5 and SBS1 observed in our IMFT cohort suggest the etiology linked with ageing and allow us to disregard the artefactual contribution from FFPE material in this study.…”
Section: Discussionmentioning
confidence: 83%
“…4e ). The COSMIC dsDNA signature SBS30 has been previously associated with NTHL1 and UNG biallelic loss of function mutations 31,59,60 and with formalin fixation 68 . NTHL1 and UNG encode DNA glycosylases that initiate base excision repair of oxidized pyrimidines, including uracil-species that result from cytosine oxidation 61,62 .…”
Section: Mainmentioning
confidence: 99%
“…The SBS5 and SBS1 signatures were highly enriched by mutations, and, notably, are both associated with aging. However, the SBS1-like signature may be caused by repair of FFPE artifacts in the process of library preparation for sequencing ( 66 ). The SBS29 signature was enriched by a quarter of all mutations and was characterized with the highest mutation burden.…”
Section: Discussionmentioning
confidence: 99%