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Immortality gene mutation identifies brain tumors and other cancers
Date:3/18/2013

ity in those diseases.

But the Duke-led research team also identified nine tumor types highly associated with TERT promoter mutations. These cancers generally share a common feature: they arise in tissues with relatively low rates of cell renewal, suggesting they require the mutation to trigger the abnormal telomerase production.

These cancer types include melanomas, liposarcomas, hepatocellular carcinomas, transitional cell carcinomas of the urinary tract, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas, including 83 percent of primary glioblastomas, the most common brain tumor in adults with a median survival of only 15 months.

"The results in brain tumors were quite striking," said Patrick J. Killela, co-lead author of the study and a Duke graduate student. "For primary glioblastoma, this is the most frequent genetic mutation yet identified in this tumor."

Four years ago, Yan's laboratory at Duke identified critical gene mutations associated with glioblastoma. But those mutations in the IDH1 and IDH2 genes -- were found only in rare glioblastomas that arose from other, lower-grade tumors known as astrocytomas and oligodendrogliomas. The main cancer-causing mutation for the other primary glioblastomas remained elusive.

"Now we see this," said Zachary J. Reitman, Ph.D., an associate in research at Duke and co-lead author of the study. "This is a major discovery in brain tumors, because this single mutation can now distinguish one tumor from another and these are tumors that are difficult to classify with a typical pathology test. For primary glioblastoma, the TERT mutation is remarkably common, while for astrocytomas, it is rare. Using both IDH1 and TERT, we can greatly improve diagnosis and prognosis."

Yan said the TERT mutations also provide a biomarker that may be useful for early detection of urinary tract and liver tumors. The finding provides new targets for drug devel
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Contact: Sarah Avery
sarah.avery@duke.edu
919-660-1306
Duke University Medical Center
Source:Eurekalert

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