Elevation of both maternal and fetal extracellular circulating deoxyribonucleic acid concentrations in the plasma of pregnant women with preeclampsia

Zhong, Xiao Yan; Laivuori, Hannele; Livingston, Jeffrey; Ylikorkala, Olavi; Sibai, Bahaeddine M; Holzgreve, Wolfgang; Hahn, Sinuhe

doi:10.1067/mob.2001.109594

Cited by 259 publications

(167 citation statements)

References 22 publications

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“…The increased release of ADAM12 mRNA into the plasma of IUGR with PET pregnant women may be related to increased placental ADAM12 mRNA expression in preeclamptic placental tissue, which is in agreement with previous studies on ADAM12 at the protein level (Gack et al, 2005). Moreover, increased concentrations of cellfree nucleic acids in PET has been reported in several studies (Lo et al, 1999;Zhong et al, 2001;Ng et al, 2003a;Purwosunu et al, 2007) and speculated to be associated with increased placental apoptosis in pregnancies complicated by PET .…”

Section: Discussionsupporting

confidence: 80%

A strategy for identifying circulating placental RNA markers for fetal growth assessment

et al. 2009

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Objective To evaluate whether circulating placental mRNAs in maternal plasma could serve as markers for the assessment of fetal growth or intrauterine growth restriction (IUGR).Methods From a panel of placental transcripts detectable in maternal plasma identified by microarray previously, we chose growth-related transcripts, namely CSH1, GH2, KISS1, and ADAM12, as potential growth markers. Relationships between the maternal plasma mRNA concentrations with several fetal growth indicators were studied. Maternal plasma mRNA concentrations from IUGR pregnancies with or without pre-eclampsia (PET) were compared with gestational age matched controls cross-sectionally and longitudinally. The four transcripts were quantified by one-step real-time RT-PCR.Results Maternal plasma GH2 mRNA significantly correlated with birth weight and fetal biometric measurements. Maternal plasma ADAM12 mRNA concentration was significantly higher in IUGR with PET than normal pregnancies in the cross-sectional comparison. No significant difference was observed for all markers between IUGR without PET and controls in both the cross-sectional and longitudinal comparisons. ConclusionThis study presents a potential strategy in identifying surrogate markers for the study of fetal growth. Circulating GH2 mRNA in maternal plasma appeared to be associated with fetal growth. The utility of this strategy and the currently assessed markers could be explored in further studies.

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Section: Discussionsupporting

confidence: 80%

A strategy for identifying circulating placental RNA markers for fetal growth assessment

et al. 2009

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“…Preeclampsia is a pregnancy related disorder and is caused by apoptotic-necrotic shedding of cell-free debris from placental ischaemia into the maternal circulation. We found that both cell-free fetal and maternal DNA was increased in the preeclampsia [20]. The increments of both the cell-free fetal and maternal DNA levels corresponded to the degree of disease severity [20].…”

Section: Discussionmentioning

confidence: 78%

“…We found that both cell-free fetal and maternal DNA was increased in the preeclampsia [20]. The increments of both the cell-free fetal and maternal DNA levels corresponded to the degree of disease severity [20]. In addition, cell-free fetal DNA increased prior to the onset of preeclampsia, but not cell-free maternal DNA [21].…”

Section: Discussionmentioning

confidence: 81%

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Elevated level of cell-free plasma DNA is associated with breast cancer

Zhong

Ladewig

Schmid

et al. 2007

Arch Gynecol Obstet

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Background We analysed cell-free DNA (cfDNA) in the plasma of patients with both malignant and benign breast lesions by real-time quantitative PCR to determine whether the Wnding may have diagnostic and prognostic implications. Methods Plasma samples were obtained from 33 patients with breast cancer, 32 patients with benign breast lesions and 50 healthy women as normal controls. Circulatory cfDNA was extracted from the plasma samples and quantiWed by real-time quantitative PCR for the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. Results The mean concentrations of cfDNA in the plasma samples from patients with breast cancer, patients with benign breast lesions and normal controls were 2,285, 1,368 and 1,489 genome equivalents (GE) per millilitre, respectively. The level of cfDNA in the breast cancer group was signiWcantly higher than those in the benign lesion group and control group (P = 0.007 and 0.013, respectively). These Wndings were associated with malignant tumour size. The levels of the cfDNA were high in patients with lymph node involvement and distant metastasis. Conclusions Our results suggest that levels of cfDNA in the plasma are elevated in malignant breast cancer and correlated with tumour size. These Wndings could have diagnostic and prognostic value for malignant breast tumours.

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“…This noninvasive source of fetal nucleic acid has already been shown to be clinically valuable in the prenatal investigation of many conditions, including fetal rhesus D status (6,7), sex-linked diseases (8), and ␤ thalassemia (9). In addition, quantitative aberrations of fetal DNA have been described in many pathological conditions, including preeclampsia (10,11), fetal chromosomal aneuploidies (12,13), and hyperemesis gravidarum (14).…”

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confidence: 99%

mRNA of placental origin is readily detectable in maternal plasma

Tsui

Lau

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

362

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The discovery of circulating fetal nucleic acid in maternal plasma has opened up new possibilities for noninvasive prenatal diagnosis. Thus far, a gender-and polymorphism-independent fetalspecific target that can be used for prenatal screening and monitoring in all pregnant women has not been reported. In addition, the origin of such circulating nucleic acid has remained unclear. Here we provide direct evidence that the placenta is an important source of fetal nucleic acid release into maternal plasma by demonstrating that mRNA transcripts from placenta-expressed genes are readily detectable in maternal plasma. The surprising stability of such placental mRNA species in maternal plasma and their rapid clearance after delivery demonstrate that such circulating mRNA molecules are practical markers for clinical use. The measurement of such plasma mRNA markers has provided a gender-independent approach for noninvasive prenatal gene expression profiling and has opened up numerous research and diagnostic possibilities.N oninvasive prenatal diagnosis is a long-sought goal in human genetics. Recent interest in cell-free DNA in plasma and serum (1, 2) has led to the discovery of fetal DNA in maternal plasma (3)(4)(5). This noninvasive source of fetal nucleic acid has already been shown to be clinically valuable in the prenatal investigation of many conditions, including fetal rhesus D status (6, 7), sex-linked diseases (8), and ␤ thalassemia (9). In addition, quantitative aberrations of fetal DNA have been described in many pathological conditions, including preeclampsia (10, 11), fetal chromosomal aneuploidies (12, 13), and hyperemesis gravidarum (14).Despite the promising clinical use of fetal DNA in maternal plasma for noninvasive prenatal diagnosis, a number of challenges remain and several fundamental biological issues about this phenomenon are unresolved. First, in studies reporting the quantitative abnormalities involving fetal DNA in maternal plasma, the Y chromosome is commonly used as a fetal-specific marker in women carrying male fetuses (10-14). The use of such Y-specific markers has limited the application of this technology to the 50% of pregnant women who are carrying male fetuses. The eventual routine clinical application of this technology, e.g., as a screening tool for fetal chromosomal aneuploidies (12, 13), will be catalyzed by the development of a gender-and polymorphism-independent fetal nucleic acid marker, which can be used in all pregnancies. Second, the source of fetal DNA in maternal plasma remains unclear. Although it has been suggested that such fetal DNA could have originated from the placenta (4), no empirical proof of this hypothesis has been put forward to date.Recently, a number of investigators have shown that in addition to DNA, RNA is also present in the plasma of human subjects, particularly those with cancer (15-18). The inherent lability of RNA has made these observations rather surprising. It has been suggested that circulating RNA may be stabilized by being protected in apoptotic ...

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Elevation of both maternal and fetal extracellular circulating deoxyribonucleic acid concentrations in the plasma of pregnant women with preeclampsia

Cited by 259 publications

References 22 publications

A strategy for identifying circulating placental RNA markers for fetal growth assessment

A strategy for identifying circulating placental RNA markers for fetal growth assessment

Elevated level of cell-free plasma DNA is associated with breast cancer

mRNA of placental origin is readily detectable in maternal plasma

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