NIH, National Cancer Institute, Division of Cancer Treatment and Diagnosis (DCTD) NIH - National Institutes of Health National Cancer Institute DCTD - Division of Cancer Treatment and Diagnosis

Logistics and quality control for DNA sampling in large multicenter studies.

Author(s): Nederhand RJ, Droog S, Kluft C, Simoons ML, de Maat MP

Publication: J Thromb Haemost, 2003, Vol. 1, Page 987-91

PubMed ID: 12871366 PubMed Review Paper? No

Purpose of Paper

The purpose of this paper was to determine the effects of storage, mechanical disruption and processing delays due to specimen shipment on hemolysis, DNA yield and quality and amplification success from blood specimens.

Conclusion of Paper

DNA yield decreased with increasing storage of blood at room temperature but DNA yield was not affected by up to 28 days of storage at 4 or -20 degrees C. For specimens stored for >3 days, the average optical density (OD)260/280 ratios were 1.7 for specimens stored at room temperature, 1.8 for specimens stored at 4 degrees C, and 1.6 for specimens stored at -20 degrees C. The authors report PCR was successful from all specimens, regardless of storage duration or temperature. The authors report visible erythrocyte lysis with increasing room temperature storage or freezing. The authors state mechanical disruption resulted in hemolysis, and lower OD260/280 ratios like those observed in specimens stored at -20 degrees C. Processing delays due to mailing specimens led to increasing hemolysis.

Studies

  1. Study Purpose

    The purpose of this study was to determine the effects of storage and mechanical disruption on the DNA yield, quality and amplification success from blood specimens. Blood was collected from 8 healthy individuals into K3EDTA tubes, and DNA was extracted by salting-out and stored at 4 degrees C. The PCR target was not specified. Mechanical disruption was conducted on a head-over vortex for 24 h or by mailing (unspecified distance, duration and temperature).

    Summary of Findings:

    DNA yield decreased with increasing storage of blood at room temperature, with a 50% reduction observed by day 28 compared to day 0, but DNA yield was not affected by up to 28 days of storage at 4 or -20 degrees C. For specimens stored for >3 days, the average OD260/280 ratios were 1.7 for specimens stored at room temperature, 1.8 for specimens stored at 4 degrees C, and 1.6 for specimens stored at -20 degrees C with more variability as well, but significance was not stated. The authors report PCR was successful from all specimens stored at room temperature, 4 degrees C, and -20 degrees C. The authors report visible erythrocyte lysis increased with increasing duration of room temperature storage which resulted in a need for repeated lysis steps and increased pronase to lyse the leukocyte pellet, but less lysis was observed with storage at 4 degrees C. The authors report that exposure of the specimens to extreme conditions (head-over vortex for 24 h, or mail for 24 h) resulted in hemolysis and variable OD260/280 ratios like those observed after storage at -20 degrees C, but similar to specimens stored at -20 degrees C there was no change in DNA yields.

    Biospecimens
    Preservative Types
    • None (Fresh)
    Diagnoses:
    • Normal
    Platform:
    AnalyteTechnology Platform
    DNA Electrophoresis
    DNA PCR
    DNA Spectrophotometry
    Cell count/volume Macroscopic observation
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(s)
    Storage Storage duration 0 days
    3 days
    7 days
    14 days
    21 days
    28 days
    Storage Storage temperature -20 degrees C
    4 degrees C
    Room temperature
    Storage Between site transportation method Mailed
    Not transported
    PCR Specific Length of gene fragment 200 bp
    1200 bp
    Biospecimen Aliquots and Components Hemolysis Not induced
    Vortex-induced
  2. Study Purpose

    The purpose of the study was to determine the effects of delayed lysis due to transport on hemolysis. This study used 11,241 specimens from a European study on the effects of perinodopril in patients with coronary artery disease. Whole blood specimens were mailed to a central laboratory in a protective box where the blood was lysed, and the leukocyte pellet was stored frozen at -20 degrees C. The delay in lysis due to storage versus transport was not specified.

    Summary of Findings:

    Increased time between blood collection and processing resulted in increased hemolysis, with the majority of specimens subjected to a delay of 5 days or more before lysis showing some hemolysis. In 93% of specimens, delays before lysis had no effect on leukocyte pellet size, and the authors report that, using a subset of 61 specimens, leukocyte pellet size was not associated with DNA yield or quality. Further, the authors report that all DNA obtained was of high molecular weight and without visible degradation, regardless of the duration of the processing delay.

    Biospecimens
    Preservative Types
    • None (Fresh)
    Diagnoses:
    • Coronary Artery Disease
    Platform:
    AnalyteTechnology Platform
    DNA Electrophoresis
    DNA Spectrophotometry
    Cell count/volume Macroscopic observation
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(s)
    Storage Storage duration 0-30 days
    Storage Between site transportation method Mailed
    Storage Specimen transport duration/condition 1-30 days

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