caa a22 4500 397573324 CHVBK 20180308164847.0 cr unu---uuuuu 161202e199608 xx s 000 0 eng 10.1093/hmg/5.8.1101 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.8.1101 Chromosome 11p15.5 Regional Imprinting: Comparative Analysis of KIP2 and H19 in Human Tissues and Wilms' Tumors [Elektronische Daten] [Wai-Yee Chung, Luwa Yuan, Lin Feng, Terrence Hensle, Benjamin Tycko] The imprinted H19 gene is frequently inactivated in Wilms' tumors (WTs) either by chromosome 11p15.5 loss of heterozygosity (LOH) or by hypermethylation of the maternal allele and it is possible that there might be coordinate disruption of imprinting of multiple 11p15.5 genes in these tumors. To test this we have characterized total and allele-specific mRNA expression levels and DNA methylation of the 11p15.5KIP2gene in normal human tissues, WTs and embryonal rhabdomyosarcoma (RMS). Both KIP2 alleles are expressed but there is a bias with the maternal allele contributing 70-90% of mRNA. Tumors with LOH show moderate to marked reductions in KIP2 mRNA relative to control tissues and residual mRNA expression is from the imprinted paternal allele. Among WTs without LOH most cases with H19 inactivation also have reduced KIP2 expression and most cases with persistent H19 expression have high levels of KIP2mRNA. In contrast to the extensive hypermethylation of the imprinted H19allele, both KIP2alleles are hypomethylated and WTs with biallelic H19 hypermethylation lack comparable hypermethylation of KIP2 DNA. 5-aza-2′-deoxycytidine (aza-C) increases H19 expression in RD RMS cells but does not activate KIP2 expression. These data indicate coordinately reduced expression of two linked paternally imprinted genes in most WTs and also suggest mechanistic differences in the maintenance of imprinting at these two loci. © 1996 Oxford University Press Chung Wai-Yee Department of Pathology, Division of Pediatric Urology, Columbia University College of Physicians and Surgeons, New York, NY, USA aut Yuan Luwa Department of Pathology, Division of Pediatric Urology, Columbia University College of Physicians and Surgeons, New York, NY, USA aut Feng Lin Department of Pathology, Division of Pediatric Urology, Columbia University College of Physicians and Surgeons, New York, NY, USA aut Hensle Terrence Department of Surgery, Division of Pediatric Urology, Columbia University College of Physicians and Surgeons, New York, NY, USA aut Tycko Benjamin Department of Pathology, Division of Pediatric Urology, Columbia University College of Physicians and Surgeons, New York, NY, USA aut Human Molecular Genetics Oxford University Press 5/8(1996-08), 1101-1108 0964-6906 5:8<1101 1996 5 hmg https://doi.org/10.1093/hmg/5.8.1101 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.8.1101 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chung Wai-Yee Department of Pathology, Division of Pediatric Urology, Columbia University College of Physicians and Surgeons, New York, NY, USA aut NATIONALLICENCE 700 1- Yuan Luwa Department of Pathology, Division of Pediatric Urology, Columbia University College of Physicians and Surgeons, New York, NY, USA aut NATIONALLICENCE 700 1- Feng Lin Department of Pathology, Division of Pediatric Urology, Columbia University College of Physicians and Surgeons, New York, NY, USA aut NATIONALLICENCE 700 1- Hensle Terrence Department of Surgery, Division of Pediatric Urology, Columbia University College of Physicians and Surgeons, New York, NY, USA aut NATIONALLICENCE 700 1- Tycko Benjamin Department of Pathology, Division of Pediatric Urology, Columbia University College of Physicians and Surgeons, New York, NY, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/8(1996-08), 1101-1108 0964-6906 5:8<1101 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford