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.

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.

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

Families who have a child or adult with pleuropulmonary blastoma or cystic nephroma are invited to participate.

Sequence data deposited in ClinVar upon publication. Publication of all final results in NIHMS