Microdeletion of target sites for insulator protein CTCF in a chromosome 11p15 imprinting center in Beckwith-Wiedemann syndrome and Wilms' tumor

Prawitt, D., Enklaar, T., Gartner-Rupprecht, B., Spangenberg, C., Oswald, M., Lausch, E., Schmidtke, P., Reutzel, D., Fees, S., Lucito, R., Korzon, M., Brozek, L., Limon, J., Housman, D. E., Pelletier, J., Zabel, B. (March 2005) Microdeletion of target sites for insulator protein CTCF in a chromosome 11p15 imprinting center in Beckwith-Wiedemann syndrome and Wilms' tumor. Proc Natl Acad Sci U S A, 102 (11). pp. 4085-4090. ISSN 0027-8424

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URL: http://www.ncbi.nlm.nih.gov/pubmed/15743916
DOI: 10.1073/pnas.0500037102

Abstract

We have analyzed several cases of Beckwith-Wiedemann syndrome (BWS) with Wilms' tumor in a familial setting, which give insight into the complex controls of imprinting and gene expression in the chromosome 11p15 region. We describe a 2.2-kbp microdeletion in the H19/insulin-like growth factor 2 (IGF2)-imprinting center eliminating three target sites of the chromatin insulator protein CTCF that we believe here is necessary, but not sufficient, to cause BWS and Wilms' tumor. Maternal inheritance of the deletion is associated with IGF2 loss of imprinting and up-regulation of IGF2 mRNA. However, in at least one affected family member a second genetic lesion (a duplication of maternal 11p15) was identified and accompanied by a further increase in IGF2 rnRNA levels 35-fold higher than control values. Our results suggest that the combined effects of the H19//GF2-imprinting center microdeletion and 11p15 chromosome duplication were necessary for manifestation of BWS.

Item Type: Paper
Uncontrolled Keywords: insulin like growth factor 2 H19 differentially methylated region GROWTH FACTOR II Growth factor II COLORECTAL CANCER Colorectal cancer BINDING SITES Binding sites MOUSE MODEL Mouse model METHYLATION Methylation IGF2 H19 GENE Gene Region REGION HYPOMETHYLATION Hypomethylation
Subjects: diseases & disorders > cancer
diseases & disorders > congenital hereditary genetic diseases
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics
CSHL Authors:
Communities: CSHL labs > Lucito lab
Depositing User: Brian Soldo
Date: March 2005
Date Deposited: 29 Mar 2012 13:42
Last Modified: 09 Nov 2017 16:45
PMCID: PMC554791
Related URLs:
URI: http://repository.cshl.edu/id/eprint/25547

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