Research Article: Whole-genome sequencing based on formalin-fixed paraffin-embedded endomyocardial biopsies for genetic studies on outcomes after heart transplantation

Date Published: June 5, 2019

Publisher: Public Library of Science

Author(s): Gustav Zar, J. Gustav Smith, Maya Landenhed Smith, Bodil Andersson, Johan Nilsson, Stanislaw Stepkowski.

http://doi.org/10.1371/journal.pone.0217747

Abstract

Whole-genome sequencing (WGS) of heart transplant recipient- and donor-derived cardiac biopsies may facilitate organ matching, graft failure prediction, and immunotolerance research. The objective of this study was to determine the feasibility of WGS based on formalin-fixed paraffin-embedded endomyocardial biopsies.

The study included serial donor- and recipient samples from patients who had undergone heart transplantation at Skane University Hospital, Lund, Sweden, between 1988 and 2009. DNA extraction and WGS were conducted. Additional WGS sequencing quality metrics and coverage were obtained with the Genome Analysis Toolkit (GATK).

The present study demonstrated the feasibility of whole-genome sequencing based on endomyocardial biopsies. This process could enable large-scale retrospective genomic studies using stored histopathological samples.

Partial Text

Post-heart transplantation survival has improved over the last three decades. Median survival now exceeds 12 years [1]. Management of long-term complications such as malignancy underscores the importance of customizing immunosuppression in transplant patients [2]. Graft failure remains the most common cause of death and is often the result of immune-mediated rejection [3].

This first of its kind study investigates the practicality of WGS analysis and the effects of storage time on formalin-fixed paraffin-embedded endomyocardial biopsies obtained from heart transplant recipients. DNA yield, coverage, and library size did not significantly decrease with FFPE storage time even up to 26 years. Previous studies have investigated the practicality of applying NGS to FFPE samples [4–9]. To the best of our knowledge, the present study is the first to test the feasibility of WGS in biopsies derived from heart transplant recipients.

This study demonstrated the feasibility of whole-genome sequencing on formalin-fixed paraffin-embedded endomyocardial biopsies and indicated that this process can facilitate large-scale studies based on stored histopathological samples.

 

Source:

http://doi.org/10.1371/journal.pone.0217747

 

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