title: MALDI-TOF mass array analysis of RASSF1A and SERPINB5 methylation patterns in human placenta and plasma.
abstract: Differences in DNA methylation patterns between placenta and blood cells of pregnant women have been suggested as potential biomarkers for noninvasive prenatal diagnostic strategies, including for common obstetrical complications, such as preeclampsia. New findings in epigenetic origins of fetal or placental disorders may improve our ability for optimal management of these conditions. Using a novel high-throughput mass spectrometry on matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass array, we compared the quantitative methylation changes of RASSF1 and SERPINB5 (also known as MASPIN) genes in placenta and plasma samples. We analyzed the methylation status of a total of 3569 CpG dinucleotides on these two genes in 83 different samples: 50 plasma samples (20 from pregnant women and 30 from nonpregnant women) and 33 placenta tissue samples (25 from normal pregnancies and eight from preeclamptic pregnancies). The aim of this study was to assess the utility of epigenetic changes as biomarkers for noninvasive prenatal diagnostic procedures. Using a two-way hierarchical cluster analysis, significantly different methylation levels of the RASSF1 gene were found between placenta (normal and preeclamptic) and plasma samples of pregnant women. Although the SERPINB5 gene was hypomethylated in placenta DNA more than in plasma DNA, it did not demonstrate significant differences between studied groups. The MALDI-TOF mass spectrometry analysis of placenta and plasma DNA methylation patterns may serve as a tool for the study of gender-independent biomarkers in noninvasive prenatal diagnosis.
authors.affiliation: Department of Cell Therapy and Regenerative Medicine, Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), Seville, Spain.
authors.forename: Maria Luz
authors.initials: ML
authors.lastname: Bellido
authors.forename: Ramin
authors.initials: R
authors.lastname: Radpour
authors.forename: Olav
authors.initials: O
authors.lastname: Lapaire
authors.forename: Isabelle
authors.initials: I
authors.lastname: De Bie
authors.forename: Irene
authors.initials: I
authors.lastname: Hösli
authors.forename: Johannes
authors.initials: J
authors.lastname: Bitzer
authors.forename: Abdelkrim
authors.initials: A
authors.lastname: Hmadcha
authors.forename: Xiao Yan
authors.initials: XY
authors.lastname: Zhong
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Holzgreve
mesh_terms: D001483:Base Sequence; D016000:Cluster Analysis; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000502:physiology; D005260:Female; D005865:Gestational Age; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010920:Placenta / Q000378:metabolism*; D010949:Plasma / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000097:blood / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods; D015843:Serpins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000097:blood / Q000235:genetics* / Q000378:metabolism
chemical_list: C411762:RASSF1 protein, human; C085344:SERPIN-B5; D015843:Serpins; D025521:Tumor Suppressor Proteins