Trial Information

Dicer1-Related Pleuropulmonary Blastoma Cancer Predisposition Syndrome: A Natural History Study

Background:

In 2009, Hill and colleagues identified heterozygous germline mutations in DICER1 in
patients with familial pleuropulmonary blastoma (PPB) 1. This disorder represents the first
reported cancer predisposition syndrome that is due to altered microRNA biogenesis.

Primary Objectives:

1. 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 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. To characterize the clinical phenotype of, and study the incident and prevalent cancer
rates in, these patients and their family members.

3. To identify differences between patients with a mutation in DICER1 who do develop
cancer and those who do not develop cancer.

4. To develop evidence-based management guidelines for PPB patients and their family.

5. To evaluate various parameters related to psychosocial and behavioral issues resulting
from being a member of a family at increased risk of PPB.

6. Create a biospecimen repository of carefully-annotated tissue samples for use in
subsequent etiologically-oriented translational research projects.

Eligibility:

- Individuals with PPB and their relatives.

- Individuals in the general population with one or more of the unique tumors reported in
patients and families with PPB: cystic nephroma, ovarian Sertoli-Leydig cell tumors,
ocular medulloepithelioma, and nasal chondromesenchymal hamartoma. Relatives of these
patients will be eligible for study enrollment as well.

Design:

Multidisciplinary natural history study with self-administered questionnaires,
clinical/epidemiologic/genetic evaluations, clinical and research laboratory tests, review
of medical records, cancer surveillance, and biospecimen acquisition: