Using postmortem formalin fixed paraffin-embedded tissues for molecular testing of sudden cardiac death: A cautionary tale of utility and limitations

Ying, Lin; Gryazeva, Tatyana; Wang, Dawei; Zhou, Bo; Um, Sung Yon; Eng, Lucy S.; Ruiter, Kevin; Rojas, Lisa; Williams, Nori; Sampson, Barbara A.; Tang, Yingying

doi:10.1016/j.forsciint.2020.110177

Cited by 10 publications

(16 citation statements)

References 11 publications

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“…The same year, Bagnall et al were the first to demonstrate the feasibility of NGS on FFPET samples from juvenile SCD cases [36]. A recent study compared results of NGS analysis of 12 SCD cases between FFPET and corresponding non-formalin fixed samples (RNA-later-preserved tissues or bloodstain card): all pathogenic variants, likely pathogenic variants or VUS identified in the nonfixed samples were also confirmed in FFPET samples with a variable degree of confidence, but the latter provided more false positives and negatives, particularly when formalin fixation was longer than 8 days [37]. Therefore, caution is advised for the use of FFPET-derived DNA for genomic studies.…”

Section: Sample Collectionmentioning

confidence: 99%

Molecular Autopsy of Sudden Cardiac Death in the Genomics Era

et al. 2021

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Molecular autopsy is the process of investigating sudden death through genetic analysis. It is particularly useful in cases where traditional autopsy is negative or only shows non-diagnostic features, i.e., in sudden unexplained deaths (SUDs), which are often due to an underlying inherited arrhythmogenic cardiac disease. The final goal of molecular autopsy in SUD cases is to aid medico-legal inquiries and to guide cascade genetic screening of the victim’s relatives. Early attempts of molecular autopsy relied on Sanger sequencing, which, despite being accurate and easy to use, has a low throughput and can only be employed to analyse a small panel of genes. Conversely, the recent adoption of next-generation sequencing (NGS) technologies has allowed exome/genome wide examination, providing an increase in detection of pathogenic variants and the discovery of newer genotype-phenotype associations. NGS has nonetheless brought new challenges to molecular autopsy, especially regarding the clinical interpretation of the large number of variants of unknown significance detected in each individual.

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Section: Sample Collectionmentioning

confidence: 99%

Molecular Autopsy of Sudden Cardiac Death in the Genomics Era

et al. 2021

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“…A study by Lin et al [31] compared variants found in FFPE cardiac tissue samples against paired whole blood samples, using HaloPlex amplification and MiSeq sequencing technology. They found both false negative and false positive variants compared to blood, but also intra-sample variation in the FFPE material, which they attributed to depth of sampling in the tissue block.…”

Section: Ffpe Artefacts -Our Findings In Relation To Othersmentioning

confidence: 99%

Technical in-depth comparison of two massive parallel DNA-sequencing methods for formalin-fixed paraffin-embedded tissue from victims of sudden cardiac death

Adolfsson

Qvick

Gréen

et al. 2021

Forensic Science International: Genetics

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“…There is an increased rate of false positives in areas not sufficiently amplified [ 25 ]. Thus, Sanger confirmation is important in all DNA extracted from blood, saliva, or fresh/frozen tissue, and crucial in DNA extracted from formalin-fixed paraffin-embedded tissue (FFPE) [ 42 ]. In DNA from FFPE fixed for more than 8 days, high ratios of both false positives and false negatives were identified, and reanalysis of samples obtained from different areas of the FFPE block is recommended.…”

Section: Technical Datamentioning

confidence: 99%

Genetic Variants as Sudden-Death Risk Markers in Inherited Arrhythmogenic Syndromes: Personalized Genetic Interpretation

Campuzano

Sarquella-Brugada

Arbelo

et al. 2020

JCM

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Inherited arrhythmogenic syndromes are the primary cause of unexpected lethal cardiac episodes in young people. It is possible that the first sign of the condition may be sudden death. Inherited arrhythmogenic syndromes are caused by genetic defects that may be analyzed using different technical approaches. A genetic alteration may be used as a marker of risk for families who carry the genetic alterations. Therefore, the early identification of the responsible genetic defect may help the adoption of preventive therapeutic measures focused on reducing the risk of lethal arrhythmias. Here, we describe the use of massive sequencing technologies and the interpretation of genetic analyses in inherited arrhythmogenic syndromes.

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Using postmortem formalin fixed paraffin-embedded tissues for molecular testing of sudden cardiac death: A cautionary tale of utility and limitations

Cited by 10 publications

References 11 publications

Molecular Autopsy of Sudden Cardiac Death in the Genomics Era

Molecular Autopsy of Sudden Cardiac Death in the Genomics Era

Technical in-depth comparison of two massive parallel DNA-sequencing methods for formalin-fixed paraffin-embedded tissue from victims of sudden cardiac death

Genetic Variants as Sudden-Death Risk Markers in Inherited Arrhythmogenic Syndromes: Personalized Genetic Interpretation

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