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Researchers identify gene implicated in neuroblastoma

A study by Mayo Clinic researchers identified that a chromosome instability gene, USP24, is frequently missing in pediatric patients with neuroblastoma. The finding provides important insight into the development of this disease, which almost exclusively affects young children.

To identify new therapeutic approaches, Paul Galardy, M.D. (PDHO ’06), Division of Pediatric Hematology/Oncology at Mayo Clinic in Rochester, and his colleagues examined the role of a set of enzymes known as deubiquitinating enzymes (DUB) in this disease. They chose this family of enzymes because they could be targeted using drug therapy.

The team identified a gene, USP24, with potential to affect the outcomes of patients with neuroblastoma and studied it to understand how it might contribute to the disease.

“Little is known about how USP24 functions,” says Dr. Galardy. “We observed low levels of USP24 in children with neuroblastoma whose tumors were highly aggressive, leading to early progression or recurrence of the disease.” He says low levels of USP24 occur commonly with other markers of aggressive disease, including amplification of the MYCN cancer gene and a loss of a large segment of chromosome 1.

The team also found that USP24 is not simply a marker for aggressive disease. Using genetically engineered mice that lack the USP24 gene, they found that USP24 plays an important role in protecting cells against errors in chromosome distribution that take place during cell division.

“When we compared cells with normal or deleted USP24 and examined the levels of proteins in dividing cells, we found that mice lacking even one of the two copies of USP24 were more prone to developing tumors,” says Dr. Galardy. “This helped lead us to our conclusion that USP24 may play a role in ensuring accurate cell division, and that a loss of USP24 in mice leads to tumor formation and may contribute to the development of aggressive neuroblastoma tumors in children.”


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