We propose to use a mouse model to investigate risk modifiers and gain insight into secondary genetic events that influence tumorigenesis in Li-Fraumeni syndrome (LFS) families harboring mutations in p53. The heterogeneity that occurs in the tumor spectrum and latency in LFS patients with inherited mutations in p53 suggest risk modifiers at loci other than the major gene. Inbred CE/J mice, which succumb to multiple types of tumors similar to those in LFS, were crossed with the p53-null 129/Sv mouse. By this Cross, we have uncovered a genetic modifier of p53, mop1, which results in embryonic lethality. Additionally, the incidence of tumors changes in these crosses. This study should provide insight as to the variability in the cancer phenotype and age of tumor onset in the human disease. Ultimately, this project will provide me with the opportunity to enhance my understanding of genetics, statistics, and developmental biology. These fields of research will aid in my long-term goal of establishing myself as an independent scientist to study the influence of risk modifiers and secondary genetic events on tumorigenesis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
3K01CA079743-03S2
Application #
7097717
Study Section
Subcommittee G - Education (NCI)
Program Officer
Lohrey, Nancy
Project Start
1999-09-01
Project End
2007-07-31
Budget Start
2001-09-01
Budget End
2007-07-31
Support Year
3
Fiscal Year
2005
Total Cost
$154,336
Indirect Cost
Name
Ohio University Athens
Department
Type
Other Domestic Higher Education
DUNS #
041077983
City
Athens
State
OH
Country
United States
Zip Code
45701
Liang, Min; Ayanga, Bernard; Du, Shuhua et al. (2008) Ovca1, a candidate gene of the genetic modifier of Tp53, Mop2, affects mouse embryonic lethality. Genes Chromosomes Cancer 47:315-25
Ayanga, Bernard; Price, Roger; Gu, Xiangjun et al. (2006) Genetic mapping of a putative tumor suppressor locus that influences tumorigenesis and metastasis in mice. Genes Chromosomes Cancer 45:668-75
Evans, Susan C; Liang, Min; Amos, Christopher et al. (2004) A novel genetic modifier of p53, mop1, results in embryonic lethality. Mamm Genome 15:415-23