Researchers at the Center for Childhood Cancer Research (CCCR), including Garrett M. Brodeur, MD, are conducting basic research into the mechanisms of malignant transformation in neuroblastoma. Some forms of neuroblastoma appear in very young children and resolve without intervention, while others undergo malignant transformation into more high-risk neuroblastoma requiring intervention. 

Researchers have discovered that the distal portion of the short arm of chromosome 1 is missing in children with malignant neuroblastoma. They suspect that CHD5, a gene located in that region, may be functioning as a tumor-suppressor gene, and that its deletion might result in the cellular proliferation resulting in the development of neuroblastoma.

Using cellular and mouse models in the laboratory, researchers are studying how loss of the gene, as well as reintroduction of the gene, affects cellular differentiation and growth. When intact, CHD5 appears to mediate cellular differentiation; when deleted, it mediates cellular proliferation. Restoring the gene pharmacologically may represent a potential therapeutic intervention for neuroblastoma.

Elucidating the underlying mechanisms of this gene will provide the necessary groundwork for the development of targeted therapeutics that lead to re-expression of CHD5.