DICER1-related Pleuropulmonary Blastoma Cancer Predisposition Syndrome: A Natural History Study
DICER1-Related Pleuropulmonary Blastoma Cancer Predisposition Syndrome: A Natural History Study
2 other identifiers
observational
1,500
1 country
2
Brief Summary
Background: \- Pleuropulmonary blastoma (PPB) is a rare fast-growing lung tumor that is associated with other, rare tumor types. Most cases of PPB appear in children younger than 6 years of age. Recently, it has been shown that this condition can be inherited (e.g., mutation of the DICER1 gene). Researchers are studying both clinical and genetic aspects of this newly described condition. They are interested in collecting further medical history and genetic information on individuals and close relatives of individuals who have PPB or other rare associated tumors. Objectives: \- To study individuals with a personal or a family history of pleuropulmonary blastoma (PPB) or other rare tumors that can be associated with PPB (e.g., cystic nephroma, nasal chondromesenchymal hamartoma, ovarian Sertoli-Leydig cell tumors, ocular medulloepithelioma). Eligibility:
- Individuals who have been diagnosed with PPB and/or PPB-related tumors.
- Close blood relatives (e.g., parents, siblings, grandparents) of individuals who have been diagnosed with PPB and/or PPB-related tumors. Design:
- Interested participants can enroll or inquire about this study by calling 1-800-518-8474.
- Participants will be asked to complete family history and medical history questionnaires. They will complete the questionnaire if they are at least 18 years of age, or another person will complete the questionnaire if the key family member is too young to do so on his or her own.
- Participants will be asked to sign a medical record release form to allow researchers to examine detailed medical history information.
- Participants may be asked to have a physical examination and imaging studies, provide blood and saliva samples, or provide tumor tissue from prior biopsies or cancer surgeries.
- Annually, participants will update the family history and individual information questionnaires to document important changes in medical history, and will also update the medical record release form. Participants may be asked to provide additional cheek lining cells and/or blood samples, as well as tumor tissue from any new or planned biopsies or tumor surgeries.
- Treatment will not be provided as part of this protocol.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 23, 2010
CompletedFirst Posted
Study publicly available on registry
November 24, 2010
CompletedStudy Start
First participant enrolled
February 13, 2011
CompletedMay 1, 2026
April 8, 2026
November 23, 2010
April 30, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Psychosocial and Behavioral Issues
To evaluate various parameters related to psychosocial and behavioral issues resulting from being a member of a family at increased risk of PPB.
On-going
Management Guidelines & Risk-reduction Strategies
To develop evidence-based management guidelines for cancer prevention and risk-reduction strategies for PPB patients and their family members prior to and after obtaining answers to the questions/objectives above.
On-going
Genetic & Environmental Interactions
To 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. These differences may include genotype/phenotype/cancer susceptibility differences, modifier genes (gene-gene interactions) and environmental risk factors (gene-environment interactions). The latter two may be informative for modification of cancer risk in the general population.
On-going
DICER1-Related Pleuropulmonary Blastoma Cancer Predisposition Syndrome
To establish a cohort of patients with PPB and/or specific neoplasms of the PPB spectrum (cystic nephroma, nasal chondromesenchymal hamartoma, ovarian Sertoli-Leydig cell and other sex cord-stromal tumors, ocular medulloepithelioma, Wilms tumor, embryonal rhabdomyosarcoma, pineoblastoma, 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.
On-going
Clinical Phenotype
To characterize the clinical phenotype of, and study the incident and prevalent cancer rates in, these patients and their family members, for all cancers combined, and for each type of cancer, and to identify and confirm the specific types of cancer and benign neoplasms associated with this disorder.
On-going
Biospecimen Repository
To create a biospecimen repository of carefully-annotated tissue samples for use in subsequent etiologically-oriented translational research projects. These samples comprise an invaluable resource for current and future studies related to the etiology of, and outcomes following, the various neoplasms that are now known, or later found to be, part of the PPB syndrome.
On-going
Secondary Outcomes (1)
Non-tumor phenotypes
On-going
Study Arms (2)
Controls
People without pathogenic DICER1 germline variation
DICER1 (cases)
People with pathogenic DICER1 germline variation or history of DICER1-associated tumors
Eligibility Criteria
A cohort of patients with PPB and/or specific neoplasms of the PPB spectrum (cystic nephroma, nasal chondromesenchymal hamartoma, ovarian Sertoli-Leydig cell and other sex cord-stromal tumors, ocular medulloepithelioma, Wilms tumor, embryonal rhabdomyosarcoma, pineoblastoma, others to be defined)
You may qualify if:
- Affected individual is defined as:
- an individual with histologically-confirmed PPB and/or other DICER1-related tumors
- an individual with a known or suspected DICER1 disease-associated variant
- an individual from the general population with one or more of the unique tumors of the types associated with DICER1 including (but not exclusively), PPB, cystic nephroma, ovarian Sertoli-Leydig cell and other sex cord-stromal tumors, ocular medulloepithelioma, nasal chondromesenchymal hamartoma, Wilms tumor, embryonal rhabdomyosarcoma, pineoblastoma, pituitary blastoma, ovarian sarcoma, CNS sarcoma and/or thyroid cancer - regardless of their family history. Additional DICER1-related neoplasms may be identified in the future, and they will be added to the protocol as needed.
- Unaffected individual is defined as:
- a family member (such as parents, siblings, children, or extended family) of an affected participant without a known or suspected DICER1 disease-associated variant or condition and they will be controls.
- All types and amounts of prior therapies are allowed.
- There is no age restriction.
- There is no restriction related to organ and marrow function.
- Ability of the individual or their legal guardian or appropriate surrogate to understand, and their willingness to provide informed consent.
- Neonates of affected individuals will be included in the Field Cohort and be eligible for genetic counseling, education, and testing, if indicated and consented by a parent/legal guardian/LAR.
You may not qualify if:
- In some instances, patients with histologically-confirmed PPB and/or another neoplasm within the DICER1-related tumor risk and their families will be referred to the Clinical Genetics Branch (CGB) by the International Pleuropulmonary Blastoma (PPB) / DICER1 Registry (IPPBR), provided that the family has previously or currently indicated a desire to be notified of such research opportunities. In non IPPBR cases, the diagnosis will be confirmed by reviewing relevant medical records and relevant surgical pathology material.
- Individuals and families referred for evaluation in whom reported diagnoses are not verifiable.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
National Cancer Institute - Shady Grove
Rockville, Maryland, 20850, United States
Related Publications (4)
Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, Jarzembowski JA, Wikenheiser-Brokamp KA, Suarez BK, Whelan AJ, Williams G, Bracamontes D, Messinger Y, Goodfellow PJ. DICER1 mutations in familial pleuropulmonary blastoma. Science. 2009 Aug 21;325(5943):965. doi: 10.1126/science.1174334. Epub 2009 Jun 25.
PMID: 19556464BACKGROUNDManivel JC, Priest JR, Watterson J, Steiner M, Woods WG, Wick MR, Dehner LP. Pleuropulmonary blastoma. The so-called pulmonary blastoma of childhood. Cancer. 1988 Oct 15;62(8):1516-26. doi: 10.1002/1097-0142(19881015)62:83.0.co;2-3.
PMID: 3048630BACKGROUNDHill DA, Jarzembowski JA, Priest JR, Williams G, Schoettler P, Dehner LP. Type I pleuropulmonary blastoma: pathology and biology study of 51 cases from the international pleuropulmonary blastoma registry. Am J Surg Pathol. 2008 Feb;32(2):282-95. doi: 10.1097/PAS.0b013e3181484165.
PMID: 18223332BACKGROUNDVasta LM, Khan NE, Higgs CP, Harney LA, Carr AG, Harris AK, Schultz KAP, McMaster ML, Stewart DR. Hematologic indices in individuals with pathogenic germline DICER1 variants. Blood Adv. 2021 Jan 12;5(1):216-223. doi: 10.1182/bloodadvances.2020002651.
PMID: 33570641DERIVED
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Douglas R Stewart, M.D.
National Cancer Institute (NCI)
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- FAMILY BASED
- Time Perspective
- OTHER
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 23, 2010
First Posted
November 24, 2010
Study Start
February 13, 2011
Last Updated
May 1, 2026
Record last verified: 2026-04-08