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Pleuropulmonary blastoma (PPB) is a rare but biologically important lung cancer of young children. Recently identified inherited genetic mutations predispose children to developing PPB, leukemia and other childhood tumors arising in the muscle, brain, ovary and kidneys. To understand how these tumors form and progress, this research uses models based upon genetic discoveries in families with hereditary PPB, by identifying the cellular events responsible for PPB initiation and progression. This is an essential step toward developing ways to detect, treat and improve outcomes for children with PPB and the related tumors associated with this inherited cancer predisposition syndrome.