DICER1 관련 흉막폐모세포종 암 소인 증후군: 자연사 연구

Study Description:

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. In 2009, Hill and colleagues identified heterozygous germline disease-associated variants in DICER1, a gene which encodes a crucial component of the microRNA processing machinery, in patients with familial pleuropulmonary blastoma (PPB). This disorder represents the first reported cancer predisposition syndrome that is due to altered microRNA biogenesis, and its discovery presents a unique and extraordinary opportunity for CGB and DCEG to play a substantial role in the development of this new area, one which is virtually certain to have etiologic ramifications far beyond those related to PPB itself.

Objectives:

1. To establish a cohort of patients with PPB and/or specific neoplasms of the DICER1-related tumor risks (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 disease-associated variants in these patients and their family members. This will also allow us to identify DICER1 disease-associated variant-negative patients who will be crucial for future gene discovery efforts.
2. 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.
3. To identify differences between patients with a germline disease-associated variant 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.
4. To develop evidence-based management guidelines for cancer prevention and risk-reduction strategies for patients with PPB and other DICER1-related tumors and their family members prior to and after obtaining answers to the questions/objectives above.
5. To evaluate various parameters related to psychosocial and behavioral issues resulting from being a member of a family at increased risk of PPB and other DICER1-related tumors.
6. 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 DICER1-related tumor risk.

Endpoints:

Primary endpoints: include all cancers, with specific attention to those currently thought to be part of the DICER1-related tumor risk.

Secondary endpoints: include non-malignant health issues.