No Evidence for Maternal–Fetal Microchimerism in Infantile Hemangioma: A Molecular Genetic Investigation

In this study, using the placental origin theory as a basis, we set out to explore whether hemangioma endothelial cells (HEC) were maternal in origin. We rigorously addressed this hypothesis using several molecular genetic techniques. Fluorescent in situ hybridization on surgical specimens of prolif...

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Published in:	Journal of investigative dermatology Vol. 126; no. 11; pp. 2533 - 2538
Main Authors:	Pittman, Kristianna M., Wolfgang Losken, H., Kleinman, Mark E., Marcus, Jeffrey R., Blei, Francine, Gurtner, Geoffrey C., Marchuk, Douglas A.
Format:	Journal Article
Language:	English
Published:	Danvers, MA Elsevier Inc 01-11-2006 Nature Publishing Elsevier Limited
Subjects:	Biological and medical sciences Chimerism Dermatology DNA, Complementary - genetics Endothelium, Vascular - chemistry Female Fetus - chemistry Fetus - pathology Genotype Glucose Transporter Type 1 - genetics Hemangioma - chemistry Hemangioma - etiology Hemangioma - pathology Humans In Situ Hybridization, Fluorescence Infant Male Medical sciences Microsatellite Repeats Placenta - chemistry Placenta - pathology Polymerase Chain Reaction Polymorphism, Single Nucleotide Pregnancy Receptors, IgG - analysis Receptors, IgG - genetics Sequence Analysis, DNA Human Dermatology Cardiovascular disease Infant Vascular disease Pregnancy Angioma Microchimerism Mother Fetus Genetics Molecular biology Child
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Summary:	In this study, using the placental origin theory as a basis, we set out to explore whether hemangioma endothelial cells (HEC) were maternal in origin. We rigorously addressed this hypothesis using several molecular genetic techniques. Fluorescent in situ hybridization on surgical specimens of proliferating hemangiomas (n=8) demonstrated no XX-labeled HEC from resected tumors of male infants. This analysis was followed by PCR genotyping of HEC (n=11) using microsatellite markers where cellular components were genotyped and compared to genomic DNA of corresponding mother–child pairs. In the seven informative mother–child pairs, HEC matched the genotype of the child and not the maternal genotype. Concerned that HEC represented a mixed population of cells, we subsequently enriched for cells using the placental-specific endothelial cell (EC) marker, FcγRII. Three informative mother–child pairs exhibited only the genotype of the child in our enriched cell population. Using sequence analysis, we identified an informative single nucleotide polymorphism in an exon of the placental-EC-specific protein, GLUT1. When comparing GLUT1 complementary DNA (cDNA) with mother–child DNA, the genotype of the cDNA matched the constitutional DNA of the child. Our results indicate that hemangiomas are not microchimeric in origin. This study provides further insight into the origin of a tumor whose pathogenesis remains elusive.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0022-202X 1523-1747
DOI:	10.1038/sj.jid.5700516