Klinisk Biokemi i Norden Nr 1, vol. 20, 2008 - page 18

18
| 1 | 2008
Klinisk Biokemi i Norden
Sammendrag
I denne korte oversiktsartikkelen redegjøres det for
et biomarkørfelt som utvikler seg hurtig. Gjennom
en blodprøve kan man få kjennskap til forandringer
i sirkulerende leucocytter intracellulære nucleinsyrer,
DNA og RNA, og til fritt DNA og RNA i plasma. Singel
Nucleotide Point mutations (SNP´s) har allerede bekr-
eftet sine muligheter som biomarkører (hemokro-
matose, cytochrom P450, CYPs). Stadig flere slike
SNPer vinner innpass i klinisk sammenheng. Siden
sirkulerende hvite blodlegemer kan sies kontinuerlig
å overvåke kroppens organer og vev og dette avspeiles
i disse blodcellers genekspresjon knyttes det i dag for-
ventninger til sykdomsspesifikke genekspresjonspro-
filer. Både ved visse kreftformer, betennelsestilstander
og hjertekar-sykdom synes hvite blodlegemer mer
eller mindre tydelig sykdomsspesifikke genekspres-
jonsprofiler. Denne type sykdomsspesifikke geneks-
presjonsmarkører vil bli økende viktig fremover. Ved
slike markører vil man kunne ha nytte av kvantitativ
måling av enkeltmarkører, og også globale genekspres-
jonsprofiler på mikro-array-plattformer. Sirkulerende
fritt DNA og kanskje særlig RNA i plasma åpner for
nye sykdomsmarkører i første rekke ved forskjellige
kreftformer og ved foeto-matenelle problemstillinger.
Oversikten gir også en henvisning til metodologiske
referanser i disse feltene.
Abstract
This short review on a rapidly expanding domain in
Biomarkers focuses on the value of markers derived
from either circulating intracellular (leukocytes) DNA
and RNA or from free DNA and RNA in plasma. In
circulating intracellular DNA biomarkers importance
Circulating nucleic acids in blood as biomarkers
Reidun Øvstebø, Peter Kierulf, Kari Bente Foss Haug.
Department of Clinical Chemistry
Ullevål University Hospital
Oslo
E-post: reidun.ovstebo@medisin.uio.no
has been pointed to receide in the ever increasing
number of SNPs directly related to disease such as
hemochromatosis or associated with genetic make up
that leads to different drug-susceptibility. Quantitative
gene expression profiling, increasingly using global
expression platforms, is gaining momentum in various
disease state such as cancer, inflammation, cardiovas-
cular disease and diabetes. Circulating free nucleic acids
in plasma or serum gain in importance as biomarkers
particularly in cancer and foeto-maternal understan-
ding. The surprising recent findings of circulating free
mRNA carries the potential of examining normal and
diseased plasma for global gene expression profiling
– opening avenues to new biomarkers. When appro-
priate this review gives reference to methodological
considerations and refers the readers to important
literature in the fields.
Introduction
In general, biomarkers aim at disclosing or monitoring
disease. So also with nucleic acids, which comprise
DNA as well as RNA. Their main working place is
within the cell, whether in fixed tissues (liver, heart
etc) or in circulating blood (white blood cells, reticulo-
cytes). In the present review we shall focus on “circu-
lating nucleic acids”, with special emphasis on blood.
We shall approach this in a dual way by focusing on
recent knowledge that may be extracted from circu-
lating white blood cells as regards both DNA (muta-
tions, hypermethylation for review (1) and RNA (gene
expression). In this latter context we shall consider
circulating white blood cells as “ambulatory surveyors
of disease”. Our second approach will be related to
circulatory extra-cellular DNA and RNA, ie. obtainable
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