ZIA CP010144 10567 (ZIA) | |||
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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 | $28,589 | Project Dates | null - null |
Fiscal Year | 2018 | 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%) |
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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 | |||
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 café-au-lait macule number; and 3) numerous publications on NF1 phenotype refinement. 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. In the past year, a manuscript on exome sequencing of NF1-associated plexiform neurofibromas has been published. A similar paper on coding changes in atypical neurofibromas is now a mature draft. Atypical neurofibromas are a poorly understood tumor like PN but with greater malignant potential. Dr. Stewart was asked to co-chair a workgroup drafting guidelines for the clinical care of adults with NF1, to be sponsored by the American College of Medical Genetics. A draft of these recommendations has been submitted to ACMG. Lastly, Dr. Stewart was on the organizing committee for a conference on the ?state-of-the-science? on MPNST, held at NIH in October 2016. This role resulted in three publications on MPNST biology (review), a proposed new scheme for MPNST pathology and a conference summary statement. |