[1722] Altered Telomeres with Loss of ATRX Protein Are Frequently Seen in High-Grade Pediatric Gliomas

Malak Abedalthagafi, Joanna Phillips, David Ellison, Alexander Judkins, Sabine Mueller, Roxanne Marshall, Daphne Haas-Kogan, Arie Perry. University of California San Francisco, San Francisco, CA; St. Jude Children's Research Hospital, Memphis, TN; University of Pennsylvania Health System, Philadelphia, PA

Background: Loss of function of alpha thalassemia/mental retardation syndrome X-linked (ATRX) protein leads to a phenotype called alternative lengthening of telomeres (ALT). Mutations that inactivate these genes are common in human pancreatic neuroendocrine tumors (PanNETs) and CNS tumors.
Design: We examined 60 cases of high-grade pediatric gliomas of various histological types and looked for loss of ATRX with immunocytochemistry and the presence of ALT with telomere-specific fluorescence in situ hybridization.
Results: Using a large cohort from multiple institution of high-grade pediatric gliomas (n = 60) we found that 33.33% of tumors were ALT positive (20/60) (Figure 1), and 75% of tumors with undetectable ATRX were positive for ALT (15/20) (Figure 2).

Conclusions: Further understanding of the role of ATRX/DAXX and histone H3.3 in GBM pathogenesis may lead to more accurate prognosis and stratification of patients to the most appropriate therapies. ALT/ATRX may serve as a potential screening and prognostic marker in patients with pediatric gliomas. Our results show that telomere-specific FISH and ATRX staining are reliable assays of choice for formalin-fixed tissue. Other genetic markers in addition to ATRX may help classify patients, leading to more accurate prognosis and more successful treatment strategies. In addition, targeting molecules that play a role in chromosome remodeling and telomere stability, including telomerase and ALT-related proteins, may be a strategy for developing new treatments for these highly aggressive pediatric cancers. Finally, our data highlight the distinction between adult and pediatric gliomas.
Category: Neuropathology

Monday, March 4, 2013 8:15 AM

Proffered Papers: Section G1, Monday Morning


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