Evidence map›Paper›PMID 37351572›Full record

ReviewNucleic acids research2023

A critical spotlight on the paradigms of FFPE-DNA sequencing.

Tim A Steiert, Genís Parra, Marta Gut, Norbert Arnold, Jean-Rémi Trotta, Raúl Tonda, Alice Moussy, Zuzana Gerber, Peter M Abuja, Kurt Zatloukal and 13 more

Abstract readReview
In one paragraph

Review in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  10. DNA Methylation-Based Risk Stratification and Classification of Pediatric Thyroid Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Tim A SteiertInstitute of Clinical Molecular Biology, Christian-Albrechts-University and University Medical Center Schleswig-Holstein, Kiel 24105, Germany.ORCID 0000-0002-0125-1173
Genís ParraCenter for Genomic Regulation, Centro Nacional de Análisis Genómico, Barcelona 08028, Spain.
Marta GutCenter for Genomic Regulation, Centro Nacional de Análisis Genómico, Barcelona 08028, Spain.
Norbert ArnoldDepartment of Gynaecology and Obstetrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel 24105, Germany.
Jean-Rémi TrottaCenter for Genomic Regulation, Centro Nacional de Análisis Genómico, Barcelona 08028, Spain.
Raúl TondaCenter for Genomic Regulation, Centro Nacional de Análisis Genómico, Barcelona 08028, Spain.
Alice MoussyLe Centre de référence, d'innovation, d'expertise et de transfert (CRefIX), PFMG 2025, Évry 91057, France.
Zuzana GerberCentre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, Évry 91057, France.
Peter M AbujaDiagnostic & Research Center for Molecular Biomedicine, Diagnostic & Research Institute of Pathology, Medical University of Graz, Graz 8010, Austria.
Kurt ZatloukalDiagnostic & Research Center for Molecular Biomedicine, Diagnostic & Research Institute of Pathology, Medical University of Graz, Graz 8010, Austria.
Christoph RöckenDepartment of Pathology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel 24105, Germany.ORCID 0000-0002-6989-8002
Trine FolseraasNorwegian PSC Research Center Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo 0372, Norway.
Marit M GrimsrudNorwegian PSC Research Center Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo 0372, Norway.
Arndt VogelDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hanover 30625, Germany.
Benjamin GoeppertInstitute of Pathology, University Hospital Heidelberg, Heidelberg 69120, Germany.
Stephanie RoesslerInstitute of Pathology, University Hospital Heidelberg, Heidelberg 69120, Germany.ORCID 0000-0002-5333-5942
Sebastian HinzDepartment of General Surgery, University Medicine Rostock, Rostock 18057, Germany.
Clemens SchafmayerDepartment of General Surgery, University Medicine Rostock, Rostock 18057, Germany.
Philip RosenstielInstitute of Clinical Molecular Biology, Christian-Albrechts-University and University Medical Center Schleswig-Holstein, Kiel 24105, Germany.
Jean-François DeleuzeLe Centre de référence, d'innovation, d'expertise et de transfert (CRefIX), PFMG 2025, Évry 91057, France.ORCID 0000-0002-5358-4463
Ivo G GutCenter for Genomic Regulation, Centro Nacional de Análisis Genómico, Barcelona 08028, Spain.ORCID 0000-0001-7219-632X
Andre FrankeInstitute of Clinical Molecular Biology, Christian-Albrechts-University and University Medical Center Schleswig-Holstein, Kiel 24105, Germany.
Michael ForsterInstitute of Clinical Molecular Biology, Christian-Albrechts-University and University Medical Center Schleswig-Holstein, Kiel 24105, Germany.ORCID 0000-0001-9927-5124

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In the late 19th century, formalin fixation with paraffin-embedding (FFPE) of tissues was developed as a fixation and conservation method and is still used to this day in routine clinical and pathological practice. The implementation of state-of-the-art nucleic acid sequencing technologies has sparked much interest for using historical FFPE samples stored in biobanks as they hold promise in extracting new information from these valuable samples. However, formalin fixation chemically modifies DNA, which potentially leads to incorrect sequences or misinterpretations in downstream processing and data analysis. Many publications have concentrated on one type of DNA damage, but few have addressed the complete spectrum of FFPE-DNA damage. Here, we review mitigation strategies in (I) pre-analytical sample quality control, (II) DNA repair treatments, (III) analytical sample preparation and (IV) bioinformatic analysis of FFPE-DNA. We then provide recommendations that are tested and illustrated with DNA from 13-year-old liver specimens, one FFPE preserved and one fresh frozen, applying target-enriched sequencing. Thus, we show how DNA damage can be compensated, even when using low quantities (50 ng) of fragmented FFPE-DNA (DNA integrity number 2.0) that cannot be amplified well (Q129 bp/Q41 bp = 5%). Finally, we provide a checklist called 'ERROR-FFPE-DNA' that summarises recommendations for the minimal information in publications required for assessing fitness-for-purpose and inter-study comparison when using FFPE samples.

Indexed as

Sequence Analysis, DNADNAFormaldehydeParaffin EmbeddingTissue FixationDNAFormaldehyde

Identifiers

PMID37351572
PMCPMC10415133

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.