The cellular protooncogene MYC encodes a nuclear transcription factor that is 
involved in regulating important cellular functions, including cell cycle 
progression, differentiation, and apoptosis. Dysregulated MYC expression appears 
critical to the development of various types of malignancies, and thus factors 
involved in regulating MYC expression may also play a key role in the 
pathogenesis of certain cancers. We have cloned one such MYC regulatory factor, 
termed CTCF, which is a highly evolutionarily conserved-11-zinc finger 
transcriptional factor possessing multiple DNA sequence specificity. CTCF binds 
to a number of important regulatory regions within the 5' noncoding sequence of 
the human MYC oncogene, and it can regulate its transcription in several 
experimental systems. CTCF mRNA is expressed in cells of multiple different 
lineages. Enforced ectopic expression of CTCF inhibits cell growth in culture. 
Southern blot analyses and fluorescence in situ hybridization (FISH) with normal 
human metaphase chromosomes showed that the human CTCF is a single-copy gene 
situated at chromosome locus 16q22. Cytogenetic studies have pointed out that 
chromosome abnormalities (deletions) at this locus frequently occur in many 
different human malignancies, suggesting the presence of one or more tumor 
suppressor genes in the region. To narrow down their localization, several loss 
of heterozygosity (LOH) studies of chromosome arm 16q in sporadic breast and 
prostate cancers have been carried out to define the most recurrent and smallest 
region(s) of overlap (SRO) for commonly deleted chromosome arm 16q material. For 
CTCF to be considered as a candidate tumor suppressor gene associated with 
tumorigenesis, it should localize within one of the SROs at 16q. Fine-mapping of 
CTCF has enabled us to assign the CTCF gene to about a 2 centiMorgan (cM) 
interval of 16q22.1 between the somatic cell hybrid breakpoints CY130(D) and 
CY4, which is between markers D16S186 (16AC16-101) and D16S496 (AFM214zg5). This 
relatively small region, containing the CTCF gene, overlaps the most frequently 
observed SROs for common chromosomal deletions found in sporadic breast and 
prostate tumors. In one of four analyzed paired DNA samples from primary breast 
cancer patients, we have detected a tumor-specific rearrangement of CTCF exons 
encoding the 11-zinc-finger domain. Therefore, taken together with other CTCF 
properties, localization of CTCF to a narrow cancer-associated chromosome region 
suggests that CTCF is a novel candidate tumor suppressor gene at 16q22.1.