ZIA CP010144 - 10567 (ZIA) | |||
---|---|---|---|
Title | Clinical and Genetic Studies of Neurofibromatosis Type 1 | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Stewart, Douglas | NCI Program Director | N/A |
Cancer Activity | N/A | Division | DCEG |
Funded Amount | $70,327 | Project Dates | 01/30/2010 - 00/00/0000 |
Fiscal Year | 2015 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Biochemical Epidemiology (45.0%) Cancer (100.0%) Neurofibromatosis (100.0%) |
Brain (50.0%) Sarcoma (50.0%) |
||
Research Type | |||
Endogenous Factors in the Origin and Cause of Cancer Interactions of Genes and/or Genetic Polymorphisms with Exogenous and/or Endogenous Factors |
|||
Abstract | |||
Neurofibromatosis type 1 (NF1) is a common genetic disorder of dysregulated cell growth. People with NF1 also develop malignant cancers. Analyses of our cohort have yielded multiple novel insights including: 1) recognition of novel tumor associations in NF1, by identifying biallelic NF1 inactivation in glomus tumors and gastrointestinal stromal tumors (GISTs); 2) identification of candidate modifier genes influencing caf?-au-lait macule number; 3) the first genome-wide association study (GWAS) in NF1; 4) numerous papers on NF1 phenotype refinement; and 5) analysis of NF1-genotype-phenotype analysis. I am using next-generation sequencing (NGS) and genomics to sequence NF1-associated tumors. We are using NGS of tumor/normal-tissue pairs to identify somatic variation (the ?neurofibrome?) that affect risk of tumorigenesis in NF1, an effort modeled upon the NCI/NHGRI Cancer Genome Atlas. Plexiform neurofibromas (PN) are congenital neurofibromas affecting up to 50% of people with NF1, which grow unpredictably and can be locally destructive. They are viewed as pre-malignant lesions from which malignant peripheral nerve sheath tumors (MPNSTs) arise. We have submitted a manuscript using exome sequencing to characterize these tumors. We have started a new project to sequence atypical neurofibromas with Eric Legius (Leuven, Belgium) and Dr. Widemann. Atypical neurofibromas are a poorly understood tumor like PN but with greater malignant potential. We are also collaborating with Dr. Widemann in a new protocol to collect PN and MPNST from the same patient. Lastly, our work on NF1 tumor sequencing has lead to collaborations to sequence meningiomas and vestibular schwannomas from patients with NF2. We published a paper this year demonstrating evidence of polyclonality in the growth of vestibular schwannomas. |