Elucidating the Genetic Basis of the Pleuropulmonary Blastoma (PPB) Familial Cancer Syndrome

Sponsor

D. Ashley Hill, M.D. (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00565903

Collaborator

(none)

2,000

Enrollment

Location

214

Duration (Months)

9.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Pleuropulmonary Blastoma (PPB) is a rare lung tumor which develops in childhood. The underlying genetic factors which contribute to the development and progression of PPB are not defined. We are working to identify the genetic factors which may contribute to the development of this rare tumor.

Condition or Disease	Intervention/Treatment	Phase
Pleuropulmonary Blastoma Cystic Nephroma Sertoli-Leydig Cell Tumor of Ovary Medulloepithelioma Embryonal Rhabdomyosarcoma of Cervix Goiter Sarcoma Pineoblastoma Pituitary Tumors Wilms Tumor

Detailed Description

Studies of inherited cancer syndromes have provided unique opportunities to uncover and explain important cellular pathways with broad relevance to both sporadic cancers and human development. This proposal studies the cancer predisposition syndrome originally described as a familial form of pleuropulmonary blastoma (PPB). PPB is a rare, aggressive lung cancer that affects young children. Children with PPB and/or their family members are at increased risk for a number of rare conditions, including Wilms tumor, rhabdomyosarcoma, brain tumors, ovarian tumors and nodular hyperplasia of the thyroid gland. In 2009, we mapped a PPB locus and identified germline, loss of function mutations in one copy of DICER1 as the genetic basis of this syndrome. DICER1 encodes a protein that performs the final critical step in maturation of microRNAs (miRNAs). miRNAs are an important form of gene regulation. The syndrome's varied nature is likely attributable to the various roles of miRNAs during different developmental and/or functional circumstances. This study focuses on defining the full phenotype of this cancer predisposition syndrome including penetrance, expressivity in children and adults, pathologic classification of disease and spectrum of predisposing DICER1 mutations. Improved understanding of the clinical and genetic features of this cancer predisposition syndrome is essential to facilitate early diagnosis when the diseases are most curable, and to create genetic counseling and educational materials to guide medical care.

Study Design

Study Type:

Observational

Anticipated Enrollment :

2000 participants

Observational Model:

Family-Based

Time Perspective:

Prospective

Official Title:

Elucidating the Genetic Basis of the Pleuropulmonary Blastoma (PPB) Familial Cancer Syndrome

Study Start Date :

Mar 1, 2005

Actual Primary Completion Date :

Dec 31, 2018

Anticipated Study Completion Date :

Dec 31, 2022

Outcome Measures

Primary Outcome Measures

Identify the genetic factors which contribute to the development or progression of pleuropulmonary blastoma [10 years]

Secondary Outcome Measures

Define the clinical features of the pleuropulmonary blastoma (PPB) familial cancer syndrome. [10 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Day to 95 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Child or adult diagnosed with pleuropulmonary blastoma, cystic nephroma, embryonal rhabdomyosarcoma of uterine cervix, ovarian Sertoli-Leydig tumor or gynandroblastoma, pineoblastoma, pituitary blastoma, nasal chondromesenchymal hamartoma, medulloepithelioma, Wilms tumor, germline or mosaic DICER1 mutation

Exclusion Criteria:

child or adult who does not fit inclusion criteria as listed above

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's National Medical Center	Washington	District of Columbia	United States	20010

Sponsors and Collaborators

D. Ashley Hill, M.D.

Investigators

Study Chair: D. Ashley Hill, MD, Children's National Research Institute
Study Director: Kris Ann Schultz, MD, Children's Hospital and Clinics of Minnesota