Methylation status of the chromosome arm 19q MicroRNA cluster in sporadic and androgenetic-Biparental mosaicism-associated hepatic mesenchymal hamartoma.
The C19MC gene on chromosome band 19q13.4 encodes a cluster of 46 microRNAs; those microRNAs are normally only expressed from the paternal allele and in the placenta. Placental expression correlates with selective demethylation of the paternal C19MC promoter, in contrast to methylation of both maternal and paternal alleles in nonplacental tissues. Prior investigations demonstrated "ectopic" activation of this gene in most hepatic mesenchymal hamartomas, including sporadic tumors and others with androgenetic-biparental mosaicism (subset of cells are diploid, but contain only paternally derived chromosomes). In the present investigation of C19MC promoter methylation status in a series of 14 mesenchymal hamartomas, a demethylated allele was identified in 6 tumors, including all 4 with androgenetic-biparental mosaicism. Conversely, only methylated alleles were cloned from sporadic hamartomas, including 3 tumors with chromosomal rearrangements thought likely to activate C19MC expression independent of the native promoter. In conjunction with published data, the findings suggest multiple molecular mechanisms for C19MC activation in hepatic mesenchymal hamartoma, including the existence of a normal placental imprinting pattern in mesenchymal cells in a subset of cases. Some or all of the latter hamartomas may result from placental "grafting," a hypothesis supported by endothelial expression of the placental vascular marker, glucose transporter-1, in 1 of the 6 cases with a demethylated allele.
Rachel B
RB
Keller
Dina El
DE
Demellawy
Alberto
A
Quaglia
Milton
M
Finegold
Raj P
RP
Kapur
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D006222:Hamartoma / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008107:Liver Diseases / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009030:Mosaicism; D005810:Multigene Family; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D035683:MicroRNAs
hamartoma; imprinting; mesenchymal dysplasia; methylation; microRNA; mosaicism; uniparental disomy