International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 87 - HAPLOINSUFFICIENCY OF CTCF LEADS TO TUMOR DEVELOPMENT IN MULTIPLE TISSUES IN MICE

Filippova G N
Fred Hutchinson Cancer Research Center

Co-Authors: Moore J M, Gurley K, Kemp C
Institutions: Fred Hutchinson Cancer Research Center

The CTCF gene encodes a zinc finger protein involved in multiple aspects of gene regulation including methylation-sensitive chromatin insulation in both normal development and cancer. Somatic missense mutations of the CTCF DNA-binding domain have been demonstrated in several human malignancies including breast, prostate and Wilms' tumors. Loss of heterozygosity at the 16q22.1 region containing the human CTCF gene is frequently observed in these tumors, but the demonstrated rate of biallelic mutations of the CTCF gene is significantly lower than the rate of loss of heterozygosity. Analysis of spontaneous and carcinogen-induced tumor development in CTCF +/- heterozygous mice, coupled with analysis of the CTCF gene and protein in the resulting tumors, revealed that haploinsufficiency of the CTCF gene results in enhanced tumor formation in multiple tissues in mice. This observation provides a potential explanation for the discordance in rates of loss of heterozygosity at 16q22.1 and CTCF mutations observed in multiple human malignancies.


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