Z01 CP010190-10374 (Z01) | |||
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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 | $392,180 | Project Dates | 02/19/2006 - N/A |
Fiscal Year | 2008 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Biochemical Epidemiology (45.0%) Cancer (100.0%) Hematology (100.0%) |
Colon/Rectum (10.0%) Head and Neck (45.0%) Leukemia (45.0%) Pharynx (45.0%) |
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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 families with dyskeratosis congenita (DC) are being conducted to 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, short telomeres and significant risk for aplastic anemia. 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 26% have TINF2, 14% DKC1, 10% TERC, 6% TERT, and no mutations NOLA2 or NOLA3 have been identified. Approximately 40% of our patients remain molecularly uncharacterized. Additional candidate gene sequencing is underway in these patients. |