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 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, Fc gammaRII. 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.
Pittman
Kristianna M
KM
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Losken
H Wolfgang
HW
Kleinman
Mark E
ME
Marcus
Jeffrey R
JR
Blei
Francine
F
Gurtner
Geoffrey C
GC
Marchuk
Douglas A
DA
D046528:Chimerism; D018076:DNA, Complementary / Q000235:genetics; D004730:Endothelium, Vascular / Q000737:chemistry; D005260:Female; D005333:Fetus / Q000737:chemistry / Q000473:pathology*; D005838:Genotype; D051272:Glucose Transporter Type 1 / Q000235:genetics; D006391:Hemangioma / Q000737:chemistry / Q000209:etiology* / Q000473:pathology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D018895:Microsatellite Repeats; D010920:Placenta / Q000737:chemistry / Q000473:pathology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D017452:Receptors, IgG / Q000032:analysis / Q000235:genetics; D017422:Sequence Analysis, DNA
D018076:DNA, Complementary; D051272:Glucose Transporter Type 1; D017452:Receptors, IgG; C495677:SLC2A1 protein, human