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Study finds clue to deadly childhood brain cancers

Thursday, February 07, 2002

By Byron Spice, Science Editor, Post-Gazette

Medical researchers have uncovered a molecular irregularity in the deadliest of brain cancers that occur in children, a first step in developing "molecular fingerprints" that would allow doctors to tailor treatments for each patient.

In a study of 231 children with brain tumors called malignant gliomas, the researchers found that children with tumors that had high levels of a protein called p53 were more likely to die than those with tumors containing low levels of p53.

Unfortunately, the outcome for both groups is poor, the researchers report in today's issue of the New England Journal of Medicine. So p53 protein levels, by themselves, aren't yet useful in guiding treatment.

But Dr. Ian Pollack, a neurosurgeon at Children's Hospital who led the study, said combining p53 levels with other molecular characteristics may finally allow doctors to distinguish the most dangerous tumors from those more readily treated, or to perhaps identify tumor subtypes that can be matched with the most appropriate treatment.

"Historically, people would classify tumors strictly by how they looked under a microscope," Pollack said. But that hasn't proven useful with gliomas, so researchers are looking for other ways of characterizing tumors. "This is, hopefully, a start in the right direction," he added.

Pollack, along with University of Pittsburgh pathologists Drs. Sydney Finkelstein and Ronald Hamilton and colleagues at five other U.S. medical centers, have been looking for other genetic and other molecular "markers" among this group of 231 brain tumor patients. He said a series of reports on these additional markers will be published over the next two or three years.

Dr. Henry S. Friedman, co-director of the Brain Tumor Center at Duke University Medical Center, said the findings also suggest that devising a drug that directly targets the p53 protein might create an effective treatment.

The p53 protein -- along with the gene that produces it -- was a logical place to start because the protein has been associated with some cancers in adults and because it has potential clinical significance. Pollack said tumors with p53 are resistant to chemotherapy and radiation, suggesting that they might need to be treated more aggressively.

In the new study, only 17 percent of the patients with high levels of p53 survived for five years, compared with 44 percent of the patients with low levels of p53.

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