Department of Pathology and Immunology Division of Anatomic Pathology D. Ashley Hill, M.D.

December 15, 2005

Dear Doctor:

I am writing to you about a collaborative study, Elucidating the genetic basis of the pleuropulmonary blastoma (PPB) familial cancer syndrome, coordinated through Washington University School of Medicine.

Pleuropulmonary blastoma (PPB) is a rare peripheral pulmonary or pleural-based mesenchymal tumor of young children. PPB is characterized in its earliest form as a multilocular cyst with small foci of mesenchymal tumor cells beneath an intact, benign epithelium (Type 1 PPB). In later stages, PPB progresses into a solid, overtly malignant neoplasm (Types II and III) that shows a variety of primitive histological patterns.

Previous studies suggest one-quarter of all affected children have a family history of benign and malignant tumors consistent with hereditary disease. These families are referred to as having the PPB familial cancer syndrome. The underlying basis for the cancer syndrome in these families is unknown.

The primary purpose of our study is to conduct a genome wide search to identify genes that may contribute to tumorigenesis in this cancer syndrome. If a candidate gene is identified, we will then conduct follow-up studies to determine what percentage of children with presumably sporadic disease have a germline mutation.

To meet this research objective, we are requesting all families with a child with pleuropulmonary blastoma consider participating in the study. Participants will not receive any direct benefit from participating, but will help to advance our understanding of this condition.

We ask if you would be so kind as to contact your families who have a child with PPB about this study. If the family is interested in learning more about the study, they may contact us, or request we contact them. If they were interested in participating, we would provide informed consent and coordinate the collection of the blood specimens.

Thank you in advance for your efforts to help us learn more about this aggressive pediatric tumor. We look forward to hearing from you soon.

Yours Sincerely,

D. Ashley Hill, M.D.

Washington University School of Medicine at Washington University Medical Center,
Box 8118, 660 S. Euclid Avenue, St. Louis, Missouri 63110-1093
Phone (314)454-8854.....Fax (314)747-2040.....hill@path.wustl.edu