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Genetic Source of Rare Childhood Cancer Found; Gene is Implicated in Other Cancers
Date:4/19/2009

r-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.

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.

The researchers also found that PPB lung tumors appear to result from a novel cancer induction mechanism not previously demonstrated. They discovered that loss of DICER1 protein specifically in lung airway cells appears to deregulate signals to nearby cells in which DICER1 itself still functions and somehow causes those cells to transform into malignant cells. However, the cells with the loss of DICER1 do not progress to malignancy.

DICER1 is so-named because its job is to chop up large molecules into smaller control molecules that help regulate the output of many of the 30,000 human genes. The short bits of genetic material it produces during its dicing activities are termed microRNAs.

"Prior research showed that the microRNA profiles of cancer cells are different from those of normal tissue, which pointed toward a possible role for DICER1 in cancer," says senior author Paul Goodfellow, Ph.D., co-director of the Hereditary Cancer Core at the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis. "Very recently, other research found that reduced DICER1 gene expression in tumor cells is associated with worse outcomes in patients with ovarian, lung, breast and prostate canc
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SOURCE Children's Hospitals and Clinics of Minnesota; Washington University School of Medicine in St. Louis; Children's National Medical Center in Washington, D.C.
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