ZIA CP010144 10548 (ZIA) | |||
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Title | DICER1-Related Pleuropulmonary Blastoma Cancer Predisposition Syndrome: A Natural | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Stewart, Douglas | NCI Program Director | N/A |
Cancer Activity | N/A | Division | DCEG |
Funded Amount | $806,243 | 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%) Childhood Cancers (60.0%) |
Eye (5.0%) Kidney Cancer (5.0%) Kidney Disease (5.0%) Lung (50.0%) Ovarian Cancer (20.0%) Pharynx (5.0%) Thyroid (10.0%) Head and Neck (10.0%) |
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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 | |||
This project is studying families with the DICER1 syndrome. This syndrome is caused by germline mutations of DICER1 and represents the first known cancer predisposition syndrome that is due to altered microRNA biogenesis. Germline mutations in DICER1 dramatically increase the risk for pleuropulmonary blastoma (PPB), a rare childhood pulmonary sarcoma. The primary goals of this study include: (1) establish a cohort of patients with PPB and/or specific neoplasms of the PPB spectrum, in order to determine the frequency of DICER1 germline mutations in these patients and their family members; (2) characterize the clinical phenotype of, and study the incident and prevalent cancer rates in these patients and their family members; (3) identify differences between patients with a germline mutation in DICER1 (or another gene(s) from this pathway) who do develop cancer and those who do not develop cancer. As of July 2017, we have evaluated a total of ~50 families (~200 individuals) at the Clinical Center with a DICER1 mutation or history of PPB in the family. In the past year, we have submitted or published work on 1) kidney phenotype in DICER1 syndrome, 2) the quantification of DICER1 variation in the population, 3) screening recommendations in DICER1 syndrome. A manuscript close to completion combines data from the NCI DICER1 cohort and two DICER1 registries to definitively establish cancer incidence and mortality standardized incidence ratio analysis of all cancer types in the syndrome. Numerous phenotype analyses and/or papers on dental, gyn, lung cyst, and eye abnormalities are underway. We are working with colleagues at Geisinger Health System to characterize DICER1 carriers in their cohort of 90K with exome sequencing. |