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Enzyme maintaining chromosome ends is linked to bone cancer recurrence, decreased survival

e lengthening of telomeres" (ALT) to maintain telomeres.

"Osteosarcoma is different from most cancers," Dome said. "Many osteosarcomas don't have telomerase and instead use ALT to maintain telomeres. We found that when these tumors do have telomerase, they are harder to cure."

The St. Jude team used tumor samples from 44 patients to determine the level of telomerase activity that existed at the time the samples were taken. The investigators measured the levels of the mRNA for a part of the telomerase enzyme called TERT, which does the actual work of building maintaining and lengthening telomeres. mRNA is the decoded form of DNA that represents the "active" form of a gene.

The team also tested for the presence of ALT in cancer cells. A total of 14 (32 percent) of the primary tumors expressed TERT mRNA. Of those, eight tumor samples expressed only TERT and six expressed TERT and activated ALT. In addition, a total of 30 (68 percent) did not express TERT mRNA. Of these 30 samples, 29 activated ALT and one had no ALT.

Among children whose tumors contained TERT, only 21 percent experienced progression-free survival (PFS) for the three years studied (that is, their cancers did not return); while among the group without TERT, 64 percent experienced PFS. Also, among those with TERT, about 43 percent survived for at least three years, compared with 70 percent whose tumor cells lacked TERT.

The researchers also studied the rate of PFS among 31 patients whose cancer had not already spread by the time they were found to have with osteosarcoma. Among those whose tumor cells contained TERT, the rate of PFS was 33 percent; while among those whose tumor cells lacked TERT, the rate of PFS was 72 percent.

Finally, among 31 children from whom tumor samples had been taken before chemotherapy began, the PFS over three years was 50 percent in those whose tumor cells contained TERT, compared to 77 percent among those without TERT.
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Contact: Bonnie Cameron
bonnie.cameron@stjude.org
901-495-4815
St. Jude Children's Research Hospital
23-Sep-2004


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