Z01 BC 010539 (Z01) | |||
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Title | Identification of Modifier Gene of Tumors Associated with NF1 and Astrocytoma | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Reilly, Karlyne | NCI Program Director | N/A |
Cancer Activity | N/A | Division | CCR |
Funded Amount | $523,755 | Project Dates | 10/01/2002 - N/A |
Fiscal Year | 2008 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Cancer (100.0%) Childhood Cancers (70.0%) Neurofibromatosis (70.0%) Neurosciences Research (70.0%) |
Brain (30.0%) Central Nervous System - Not Including Brain (70.0%) Nervous System (70.0%) Sarcoma (30.0%) Sarcoma, Soft (Sarcoma Subset) (30.0%) |
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Research Type | |||
Endogenous Factors in the Origin and Cause of Cancer Interactions of Genes and/or Genetic Polymorphisms with Exogenous and/or Endogenous Factors |
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Abstract | |||
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 (MPNSTs) 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. During fiscal year 2008, we have tested expression differences in several candidate modifiers affecting MPNSTs and have found strain-specific differences in several. We have demonstrated that both imprinted factors on mouse chromosome 11 and the gender of the mouse alter how modifiers act. Through these studies we are beginning to build up networks of genetic interactions affecting susceptibility. We have furthermore gathered evidence that an imprinted gene on mouse chromosome 11 acts in a haploinsufficient, tumor suppressive manner when mutated in our model system. Further study of this gene in the upcoming years may elucidate the mechanism of inherited susceptibility/resistance. We have completed a large scale genotyping of 1400 SNPs on 600 samples in collaboration with the Center for Inherited Disease Research that will be used in the upcoming year to map modifier loci affecting resistance to astrocytoma. |