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 | $1,001,922 | Project Dates | 09/15/2009 - 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%) Childhood Cancers (60.0%) |
Eye (5.0%) Kidney Disease (5.0%) Lung (40.0%) Ovarian Cancer (20.0%) Thyroid (20.0%) Head and Neck (10.0%) Kidney Cancer (5.0%) Pharynx (5.0%) |
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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 pleuropulmonary blastoma (PPB). This syndrome is caused by germline mutations of DICER1 and represents the first known cancer predisposition syndrome that is due to altered microRNA biogenesis. The primary goals of this study include: (1) establish a cohort of patients with PPB and/or specific neoplasms of the PPB spectrum (cystic nephroma, nasal chondromesenchymal hamartoma, ovarian Sertoli-Leydig cell tumors, ocular medulloepithelioma, others to be defined), 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 August 2015, we have evaluated a total of 32 families (157 individuals) at the Clinical Center with a DICER1 mutation or history of PPB in the family. In the past year, a survival analysis of the 350 cases from the International PPB Registry was published. Using data collected from families evaluated at the Clinical Center, we are currently working on a comprehensive analysis of endocrine, dental, genito-urinary abnormalities in DICER1 carriers. This project will also include a report on DICER1 second hits in thyroid tissues in PPB families. We are also conducting a standardized incidence ratio analysis of all cancer types in our cohort. We worked with extramural colleagues to submit a UO1 grant. |