Studies of families with neurofibromatosis type 1 (NF1) have demonstrated that the severity of this disease depends on modifier genes in the individuals. We are using a mouse model of the malignancies associated with NF1 in which the Nf1 and p53 gene are mutated on the same chromosome and screening for modifier genes in different strains of mice. We have recently identified a region responsible for resistance to developing malignant peripheral nerve sheath tumors in one strain of mice, and another region responsible for susceptibility to astrocytoma. We are working to identify candidate modifier genes within these regions that can be tested for their role in tumorigenesis in our mouse model and then in human cancers.

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010539-03
Application #
7291902
Study Section
(MCGP)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2005
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Tuskan, Robert G; Tsang, Shirley; Sun, Zhonghe et al. (2008) Real-time PCR analysis of candidate imprinted genes on mouse chromosome 11 shows balanced expression from the maternal and paternal chromosomes and strain-specific variation in expression levels. Epigenetics 3:43-50
Hawes, Jessica J; Tuskan, Robert G; Reilly, Karlyne M (2007) Nf1 expression is dependent on strain background: implications for tumor suppressor haploinsufficiency studies. Neurogenetics 8:121-30
Reilly, Karlyne M; Broman, Karl W; Bronson, Roderick T et al. (2006) An imprinted locus epistatically influences Nstr1 and Nstr2 to control resistance to nerve sheath tumors in a neurofibromatosis type 1 mouse model. Cancer Res 66:62-8
Reilly, Karlyne M; Tuskan, Robert G; Christy, Emily et al. (2004) Susceptibility to astrocytoma in mice mutant for Nf1 and Trp53 is linked to chromosome 11 and subject to epigenetic effects. Proc Natl Acad Sci U S A 101:13008-13
Stemmer-Rachamimov, Anat O; Louis, David N; Nielsen, Gunnlaugur P et al. (2004) Comparative pathology of nerve sheath tumors in mouse models and humans. Cancer Res 64:3718-24
Reilly, Karlyne M (2004) The importance of genome architecture in cancer susceptibility: location, location, location. Cell Cycle 3:1378-82