Deleterious effects of formalin-fixation and delays to fixation on RNA and miRNA-Seq profiles.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
06 05 2019
Historique:
received: 07 01 2019
accepted: 08 04 2019
entrez: 8 5 2019
pubmed: 8 5 2019
medline: 24 10 2020
Statut: epublish

Résumé

The National Cancer Institute conducted the Biospecimen Pre-analytical Variables (BPV) study to determine the effects of formalin fixation and delay to fixation (DTF) on the analysis of nucleic acids. By performing whole transcriptome sequencing and small RNA profiling on matched snap-frozen and FFPE specimens exposed to different delays to fixation, this study aimed to determine acceptable delays to fixation and proper workflow for accurate and reliable Next-Generation Sequencing (NGS) analysis of FFPE specimens. In comparison to snap-freezing, formalin fixation changed the relative proportions of intronic/exonic/untranslated RNA captured by RNA-seq for most genes. The effects of DTF on NGS analysis were negligible. In 80% of specimens, a subset of RNAs was found to differ between snap-frozen and FFPE specimens in a consistent manner across tissue groups; this subset was unaffected in the remaining 20% of specimens. In contrast, miRNA expression was generally stable across various formalin fixation protocols, but displayed increased variability following a 12 h delay to fixation.

Identifiants

pubmed: 31061401
doi: 10.1038/s41598-019-43282-8
pii: 10.1038/s41598-019-43282-8
pmc: PMC6502812
doi:

Substances chimiques

Fixatives 0
MicroRNAs 0
Formaldehyde 1HG84L3525
RNA 63231-63-0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

6980

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Auteurs

Wendell Jones (W)

Q2 Solutions - EA Genomics, Morrisville, NC, USA. Wendell.Jones@q2labsolutions.com.

Sarah Greytak (S)

Kelly Government Solutions, Rockville, MD, USA.

Hana Odeh (H)

National Cancer Institute, Bethesda, MD, USA.

Ping Guan (P)

National Cancer Institute, Bethesda, MD, USA.

Jason Powers (J)

Q2 Solutions - EA Genomics, Morrisville, NC, USA.

Jasmin Bavarva (J)

Leidos Biomedical Research, Inc, Frederick, MD, USA.

Helen M Moore (HM)

National Cancer Institute, Bethesda, MD, USA.

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Classifications MeSH