Genetic Source of  Pleuropulmonary Blastoma Found

Gene Mutation Discovery Leads to Early Detection of PPB

The search for the cause of an inherited form of a rare, aggressive childhood lung cancer has uncovered important information about how the cancer develops and potentially sheds light on the development of other cancers. Children’s physicians, Dr. Yoav Messinger and Dr. Jack Priest partnered with colleagues at Children’s of St. Louis and Children’s National in the discovery that some children with the rare cancer pleuropulmonary blastoma (PPB) are born with a deleterious mutation in the DICER1 gene.

We are thrilled (to have)…uncovered an important mutation and we have begun to understand the cellular mix-up which results in malignancy,” said Jack Priest, M.D., research director of the International PPB Registry at Children’s Hospitals and Clinics of Minnesota.

Only 50 to 60 cases of PPB are diagnosed each year around the world. Most children with PPB are under five years of age.  The cancer progresses from air-filled lung cysts in the early stage to solid lung tumors in later stages. If detected in the earliest stage, 90 percent of patients appear to be cured when treated with surgery and sometimes chemotherapy. Overall survival drops to about 40 percent if the cancer is diagnosed in the latest stage. “Having identified this gene will allow us to focus on early detection on the children who are most susceptible," stated Children’s Dr. Yoav Messinger.

The researchers found that all the children studied with PPB carried damaging mutations in one of their DICER1 genes, giving them one functional and one nonfunctional DICER1 gene in all their body's cells. The researchers indicate that PPB lung tumors probably originate when one or more cells in the lung acquire a harmful mutation in their functional copy of the DICER1 gene.

PPB Registry Facilitates Family Connections

In the summer of 2008, 31 families gathered in Minneapolis from across the United States and as far away as Australia, Ireland and Canada to share a sense of hope. Virtually connected through the PPB Registry web site, they were now having the chance to meet face to face.  What did they have in common? Their children had all beaten the odds and survived PPB. The PPB Registry is the only international resource to offer diagnosis, treatment, and surveillance information for both providers and families.