Inherited mutations identified in familial pleuropulmonary blastoma

21 Apr 2009

Children who inherit a mutated copy of the DICER1 gene may be predisposed to pleuropulmonary blastoma, a rare form of lung cancer. 

Dr. Dana Ashley Hill, chief of anatomic pathology at Children’s National Medical Center in Washington, D.C., speaking at the AACR Annual Meeting, said pediatric cases of pleuropulmonary blastoma are extremely rare, with only about 25 to 35 cases reported each year in the United States. Hill said this was the first time scientists have identified a genetic mutation in one cell type that drives cancer formation in a different cell type. 

"This study is an example of the advances that can be made in the study of a rare disease, and it will help physicians who are very likely encountering their first case of pleuropulmonary blastoma," she said. "It helps not only those families with the disease, but sheds light on important biological mechanisms." 

Pleuropulmonary blastoma arises during fetal development, and the majority of patients who have the disease are diagnosed before 6 years old. More than 25 per cent of children who have this disease report a family history. For the current study, Hill and colleagues analysed four families that included 14 clinically affected members.

Researchers identified 10 sequence defects in the DICER1 gene that all appeared to be loss of function mutations. All family members had these mutations in common. Hill said in a normal genetic make-up, DICER1 would contribute to the development of lung tissue. Its loss of function leads to the malignancy characterised by pleuropulmonary blastoma. 

"These cells that lose DICER1 are deregulated in such a manner that they now direct adjacent cells to proliferate uncontrollably and that predisposes these adjacent cells to develop additional genetic abnormalities and become cancerous," said Hill.