ZIA CP010190 10374 (ZIA) | |||
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Title | Dyskeratosis Congenita | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Savage, Sharon | NCI Program Director | N/A |
Cancer Activity | N/A | Division | DCEG |
Funded Amount | $66,363 | Project Dates | 02/19/2006 - N/A |
Fiscal Year | 2010 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Biochemical Epidemiology (45.0%) Cancer (100.0%) |
Buccal Cavity (20.0%) Colon/Rectum (10.0%) Leukemia (20.0%) Pharynx (20.0%) |
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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 | |||
Comprehensive clinical and molecular evaluations of patients with dyskeratosis congenita (DC) and their family members are being conducted to better understand the role of telomere biology defects in this disorder. DC is an inherited bone marrow failure syndrome (IBMFS) characterized by abnormal nails, lacey reticular pigmentation, oral leukoplakia, very short telomeres, and significantly elevated risks of aplastic anemia and cancer. Family pedigrees in DC indicate that there are multiple modes of inheritance (e.g. X-linked, autosomal dominant and autosomal recessive), although many cases are sporadic with no known cause. We identified a new gene which causes autosomal dominant DC, TINF2, which is a component of the shelterin complex of telomere protection proteins. All families with DC enrolled in the NCI?s IBMFS study are evaluated for mutations in the known DC genes, TINF2, DKC1, TERC, TERT, NOLA2, and NOLA3. In our cohort 28% have TINF2, 17% DKC1, 10% TERC, 7% TERT, and no mutations NOLA2 or NOLA3 have been identified. Approximately 40% of our patients remain molecularly uncharacterized. We have identified a potential new dyskeratosis congenita gene that is important in telomere biology. The functional studies are currently underway. We are also evaluating the role of copy number variants in dyskeratosis congenita and developing collaborations on exome sequencing. New hypotheses are being explored which include the epigenetic regulation of telomere length and presence of chromosomal abnormalities in DC. Detailed characterization of the clinical features of DC, including medical problems, psychiatric problems, and complications related to hematopoietic stem cell transplant is ongoing within our DC cohort |