Detection of the placental epigenetic signature of the
            <i>maspin</i>
            gene in maternal plasma

Chim, Stephen S.C.; Yu, Tong; Chiu, Rossa W.K.; Lau, Tze Kin; Leung, Tse Ngong; Chan, Lisa; Oudejans, Cees B.M.; Ding, Chunming; Lo, Y.M. Dennis

doi:10.1073/pnas.0503335102

Cited by 311 publications

(250 citation statements)

References 29 publications

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“…Apart from placental-specific mRNA transcripts, other types of fetal-specific nucleic acid species in maternal plasma could be used. One example is fetal epigenetic markers (12,21) which have recently been used for the noninvasive prenatal detection of trisomy 18 via the epigenetic allelic ratio (EAR) approach (10). Thus, we predict that digital EAR would be a possible analytical technique.…”

Section: Discussionmentioning

confidence: 99%

“…Significant developments have recently been made (9)(10)(11). One approach focuses on the detection of nucleic acid species that are fetal-specific, including DNA fragments with a placenta-specific DNA methylation pattern (10,12) and RNA molecules expressed by the placenta (9). Because circulating fetal nucleic acids are mainly derived from the placenta, the problem of maternal background interference can be overcome by targeting such molecules in maternal plasma (4).…”

mentioning

confidence: 99%

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Digital PCR for the molecular detection of fetal chromosomal aneuploidy

Lun²,

Chan³

et al. 2007

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

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Trisomy 21 is the most common reason that women opt for prenatal diagnosis. Conventional prenatal diagnostic methods involve the sampling of fetal materials by invasive procedures such as amniocentesis. Screening by ultrasonography and biochemical markers have been used to risk-stratify pregnant women before definitive invasive diagnostic procedures. However, these screening methods generally target epiphenomena, such as nuchal translucency, associated with trisomy 21. It would be ideal if noninvasive genetic methods were available for the direct detection of the core pathology of trisomy 21. Here we outline an approach using digital PCR for the noninvasive detection of fetal trisomy 21 by analysis of fetal nucleic acids in maternal plasma. First, we demonstrate the use of digital PCR to determine the allelic imbalance of a SNP on PLAC4 mRNA, a placenta-expressed transcript on chromosome 21, in the maternal plasma of women bearing trisomy 21 fetuses. We named this the digital RNA SNP strategy. Second, we developed a nonpolymorphism-based method for the noninvasive prenatal detection of trisomy 21. We named this the digital relative chromosome dosage (RCD) method. Digital RCD involves the direct assessment of whether the total copy number of chromosome 21 in a sample containing fetal DNA is overrepresented with respect to a reference chromosome. Even without elaborate instrumentation, digital RCD allows the detection of trisomy 21 in samples containing 25% fetal DNA. We applied the sequential probability ratio test to interpret the digital PCR data. Computer simulation and empirical validation confirmed the high accuracy of the disease classification algorithm.circulating fetal nucleic acids ͉ noninvasive prenatal diagnosis ͉ sequential probability ratio test ͉ trisomy 21 ͉ RNA SNP

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Digital PCR for the molecular detection of fetal chromosomal aneuploidy

Lun²,

Chan³

et al. 2007

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

Self Cite

390

328

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“…A recent study has indicated differential DNA methylation of the maspin gene between the placenta and maternal blood cells (24), which could potentially be exploited to develop further markers for noninvasive prenatal assessment. Examination of paired placental tissues and maternal blood cells from pregnant women identified hypomethylation of maspin promoter in placental tissues compared with its densely methylated status in maternal blood cells.…”

Section: Prospective Usefulness Of Maspin In Diagnosismentioning

confidence: 99%

“…24). This intriguing difference might assist in deciphering the regulatory mechanism(s) governing tissue-specific methylation of maspin and perhaps certain other genes.…”

Section: Maspin Gene Regulation Dna Methylation and Histone Methylamentioning

confidence: 99%

Maspin: The New Frontier

Khalkhali‐Ellis

2006

Clinical Cancer Research

113

117

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Maspin (mammary serine protease inhibitor) was identified in 1994 by subtractive hybridization analysis of normal mammary tissue and breast cancer cell lines. Subsequently, emerging evidence portrays maspin as a multifaceted protein, interacting with diverse group of intercellular and extracellular proteins, regulating cell adhesion, motility, apoptosis, and angiogenesis and critically involved in mammary gland development. The tissue-specific expression of maspin is epigenetically controlled, and aberrant methylation of maspin promoter is closely associated with maspin gene silencing. Identification of new tissue sites expressing maspin and novel maspin-binding partners has expanded the horizon for maspin research and promises maspin-based therapeutic approaches for combating cancer. This perspective briefly outlines the past and present strides in deciphering this unique molecule and speculates on new frontiers in maspin research and prospects of maspin as a diagnostic/prognostic indicator in cancer.The serine protease inhibitor superfamily (serpins) is categorized to inhibitory and noninhibitory serpins (1). Inhibitory serpins use their reactive center loop to trap the target proteinase and inhibit its activity (1). The noninhibitory serpins have shorter NH 2 and COOH termini, and they also lack the classic serpin secretory signal peptide (1). Recent studies indicate serpins function beyond their serpin properties: they are involved in cell adhesion and play a role in extracellular matrix remodeling (2).Maspin (mammary serine protease inhibitor) shares sequence homology with inhibitory serpins, such as plasminogen activator inhibitors 1 and 2, a-1 anti-trypsin, and noninhibitory serpin ovalbumin (3), and several recent sequence comparisons seem to suggest that maspin is more closely related to noninhibitory clade B serpins. The reactive center loop of maspin is significantly shorter than that of most inhibitory serpins, and maspin does not undergo conformational rearrangement required to inactivate target protease(s) (4). However, the reactive center loop of maspin is clearly important for its function; studies using synthetic maspin reactive center loop peptides and maspin/ovalbumin chimeras reveal that this region is important for promoting cell adhesion (5).In the past decade, with the expansion of studies on maspin, novel protein-binding partners have been identified and provided insight into the molecular aspects of its regulation and its divergent mechanism of action. More importantly, they have presented new prospects for therapeutic interventions for breast, prostate, and many other cancers.

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“…This is the rationale for minimally-invasive genetic diagnoses of fetal aneuploidies (such as Down's syndrome), using a peripheral blood sample from the mother [13].…”

Section: Introductionmentioning

confidence: 99%

Methylation of the imprinted GNAS1 gene in cell-free plasma DNA: equal steady-state quantities of methylated and unmethylated DNA in plasma

Puszyk

Chatha

Elsenheimer

et al. 2009

Clinica Chimica Acta

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However, the production and clearance of cell-free DNA from plasma in relation to its methylation status, are poorly understood processes. Methods:We studied the methylation status of DNA derived from the imprinted GNAS1 locus, in cell-free plasma DNA of healthy adults. Heterozygotes were identified that carried the SNP rs1800905 in the imprinted region. The parent-oforigin-dependent DNA methylation was analysed by bisulfite conversion, followed by cloning and sequencing.Results: Genomic DNA molecules derived from both the methylated, maternal, allele and the unmethylated, paternal, allele were found in plasma. Methylated and unmethylated DNA molecules were present in equal numbers. Conclusions:Our data indicate that the methylation status of a DNA sequence has no effect on its steady state concentration in the cell-free DNA component of plasma, in healthy adults.2

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Detection of the placental epigenetic signature of the maspin gene in maternal plasma

Cited by 311 publications

References 29 publications

Digital PCR for the molecular detection of fetal chromosomal aneuploidy

Digital PCR for the molecular detection of fetal chromosomal aneuploidy

Maspin: The New Frontier

Methylation of the imprinted GNAS1 gene in cell-free plasma DNA: equal steady-state quantities of methylated and unmethylated DNA in plasma

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