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 | $668,605 | Project Dates | 00/00/0000 - 00/00/0000 |
Fiscal Year | 2013 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Biochemical Epidemiology (45.0%) Cancer (100.0%) Childhood Cancers (60.0%) |
Pharynx (5.0%) Eye (5.0%) Kidney Cancer (5.0%) Kidney Disease (5.0%) Lung (40.0%) Ovarian Cancer (5.0%) Testes (5.0%) Thyroid (5.0%) |
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Research Type | |||
Endogenous Factors in the Origin and Cause of Cancer | |||
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 2013, we have evaluated 20 families (75 individuals) at the Clinical Center with a DICER1 mutation or history of PPB in the family. Dr. Stewart presented results during a platform session at the 2012 meeting of the American Society of Human Genetics. He also hosted a meeting of the project investigators in January 2013. A GeneReviews chapter on DICER1/PPB (with Dr. Stewart as a co-author) will be published this year. Publications to be expected in 2013-2014: 1) on survival analysis of the 350 cases from the International PPB Registry, 2) report of second hits in DICER1 in DICER1-associated nasal tumors, and 3) a survey of pathology and DICER1 status (second hits) in thyroid tissues in PPB families. An abstract on PPB survival has been accepted to the 2013 meeting of the American Society of Human Genetics. |