ZIA CP010144 - 10548 (ZIA) | |||
---|---|---|---|
Title | DICER1-Related Pleuropulmonary Blastoma Cancer Predisposition Syndrome: A Natural History Study | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Stewart, Douglas | NCI Program Director | N/A |
Cancer Activity | N/A | Division | DCEG |
Funded Amount | $799,827 | Project Dates | 09/15/2009 - 00/00/0000 |
Fiscal Year | 2014 | 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%) Head and Neck (10.0%) Kidney Cancer (25.0%) Kidney Disease (25.0%) Lung (40.0%) Ovarian Cancer (10.0%) Pharynx (5.0%) Testes (5.0%) Thyroid (5.0%) |
||
Research Type | |||
Endogenous Factors in the Origin and Cause of Cancer Interactions of Genes and/or Genetic Polymorphisms with Exogenous and/or Endogenous Factors |
|||
Abstract | |||
This project is studying families with pleuropulmonary blastoma (PPB). This newly described 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. This will also allow us to identify DICER1 mutation-negative patients who will be crucial for future gene discovery efforts; (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 2014, we have evaluated 30 families (115 individuals) at the Clinical Center with a DICER1 mutation or history of PPB in the family. In the past year, a GeneReviews chapter on DICER1/PPB (with Dr. Stewart as a co-author) was published, as was a short case report. A report of second hits in DICER1 in DICER1-associated nasal tumors was accepted for publication. A survival analysis of the 350 cases from the International PPB Registry is currently under review. Using data collected from families evaluated at the Clinical Center, we are currently working on a comprehensive analysis of endocrine abnormalities in DICER1 carriers. This project will also include a report on DICER1 second hits in thyroid tissues in PPB families. With colleagues at Children?s National Medical Center we are collaborating on a survey of thyroid pathology in DICER1 individuals. " |