ABSTRACT
OBJECTIVE: Our objective was to determine whether there were significant differences in genome-wide DNA methylation in newborns with major congenital heart defect (CHD) compared to controls. We also evaluated methylation of cytosines in CpG motifs for the detection of these CHDs. METHODS: Genome-wide DNA methylation analysis was performed on DNA from 60 newborns with various CHDs, including hypoplastic left heart syndrome, ventricular septal deficit, atrial septal defect, pulmonary stenosis, coarctation of the aorta and Tetralogy of Fallot, and 32 controls. RESULTS: Highly significant differences in cytosine methylation were seen in a large number of genes throughout the genome for all CHD categories. Gene ontology analysis of CHD overall indicated over-represented biological processes involving cell development and differentiation, and anatomical structure morphogenesis. Methylation of individual cytosines in CpG motifs had high diagnostic accuracy for the detection of CHD. For example, for coarctation one predictive model based on levels of particular cytosine nucleotides achieved a sensitivity of 100% and specificity of 93.8% (AUC = 0.974, p < 0.00001). CONCLUSION: Profound differences in cytosine methylation were observed in hundreds of genes in newborns with different types of CHD. There appears to be the potential for development of accurate genetic biomarkers for CHD detection in newborns.
Subject(s)
DNA Methylation , Heart Defects, Congenital/etiology , Biomarkers , Case-Control Studies , Epigenesis, Genetic , Gene Ontology , Heart Defects, Congenital/diagnosis , Humans , Infant, NewbornABSTRACT
BACKGROUND: Chemoradiation is an alternative to radical vulvectomy with en bloc node dissection for advanced vulvar cancer. We report a case of complete clinical and pathologic response with chemotherapy alone in a patient with advanced vulvar cancer. CASE: A middle-aged woman known to have had human immunodeficiency virus (HIV) for 10 years was newly diagnosed with advanced-stage squamous carcinoma of the vulva. She was treated with a total of nine cycles of platinum-based combination chemotherapy, with complete clinical and pathologic response. She remains in complete clinical remission without evidence of recurrent disease by noninvasive testing in the absence of any further therapy 24 months after her last chemotherapy treatment. CONCLUSION: Platinum-based combination chemotherapy may be used successfully for patients with advanced-stage squamous carcinoma of the vulva.
