The applicant has discovered a novel candidate tumor suppressor gene, called CTCF, which is a major strictly evolutionarily conserved, negative regulator of vertebrate c-myc genes. The human CTCF gene is situated at chromosome 16q band 22, the locus of chromosome abnormalities frequently found in several human cancers particularly sporadic breast carcinomas. It is rearranged in certain breast cancer cell lines and primary tumors. Since allelic imbalance on 16q occurs in two thirds of sporadic breast cancers, and loss of chromosome arm 16q is an early event in breast tumorigenesis, the principal investigator believes that loss of normal CTCF functioning, resulting in aberrant regulation of the c-myc proto-oncogene, is likely to be the critical event in breast cancer. The major goal of this proposal is to establish a connection between CTCF gene abnormal structure and/or expression and breast cancers. The principal investigator has already obtained a clear example of a tumor-specific CTCF rearrangement in a primary breast cancer patient. To characterize an association of CTCF mutations and breast tumorigenesis in detail, the principal investigator has isolated the human genomic CTCF locus, completed DNA sequencing of all exon-intron junctions, and have designed DNA primers to use standard combination of PCR and SSCP [single-strand conformation polymorphism] and DNA sequencing for detection of CTCF gene mutations in breast cancer. Identification of CTCF as a new tumor suppressor gene could be of major importance for understanding molecular mechanisms of sporadic breast tumorigenesis and, potentially, for the development of breast cancer diagnostic and prognostic possibilities.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA071732-03
Application #
2733263
Study Section
Chemical Pathology Study Section (CPA)
Program Officer
Marks, Cheryl L
Project Start
1996-07-15
Project End
2000-06-30
Budget Start
1998-07-01
Budget End
2000-06-30
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109