Browsing by Author "Diaz, Luis A"

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Open Access
Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas.
(Oncotarget, 2012-07) Jiao, Yuchen; Killela, Patrick J; Reitman, Zachary J; Rasheed, Ahmed B; Heaphy, Christopher M; de Wilde, Roeland F; Rodriguez, Fausto J; Rosemberg, Sergio; Oba-Shinjo, Sueli Mieko; Nagahashi Marie, Suely Kazue; Bettegowda, Chetan; Agrawal, Nishant; Lipp, Eric; Pirozzi, Christopher; Lopez, Giselle; He, Yiping; Friedman, Henry; Friedman, Allan H; Riggins, Gregory J; Holdhoff, Matthias; Burger, Peter; McLendon, Roger; Bigner, Darell D; Vogelstein, Bert; Meeker, Alan K; Kinzler, Kenneth W; Papadopoulos, Nickolas; Diaz, Luis A; Yan, Hai
Mutations in the critical chromatin modifier ATRX and mutations in CIC and FUBP1, which are potent regulators of cell growth, have been discovered in specific subtypes of gliomas, the most common type of primary malignant brain tumors. However, the frequency of these mutations in many subtypes of gliomas, and their association with clinical features of the patients, is poorly understood. Here we analyzed these loci in 363 brain tumors. ATRX is frequently mutated in grade II-III astrocytomas (71%), oligoastrocytomas (68%), and secondary glioblastomas (57%), and ATRX mutations are associated with IDH1 mutations and with an alternative lengthening of telomeres phenotype. CIC and FUBP1 mutations occurred frequently in oligodendrogliomas (46% and 24%, respectively) but rarely in astrocytomas or oligoastrocytomas ( more than 10%). This analysis allowed us to define two highly recurrent genetic signatures in gliomas: IDH1/ATRX (I-A) and IDH1/CIC/FUBP1 (I-CF). Patients with I-CF gliomas had a significantly longer median overall survival (96 months) than patients with I-A gliomas (51 months) and patients with gliomas that did not harbor either signature (13 months). The genetic signatures distinguished clinically distinct groups of oligoastrocytoma patients, which usually present a diagnostic challenge, and were associated with differences in clinical outcome even among individual tumor types. In addition to providing new clues about the genetic alterations underlying gliomas, the results have immediate clinical implications, providing a tripartite genetic signature that can serve as a useful adjunct to conventional glioma classification that may aid in prognosis, treatment selection, and therapeutic trial design.
Open Access
Imaging of musculoskeletal bacterial infections by [124I]FIAU-PET/CT.
(PLoS One, 2007-10-10) Diaz, Luis A; Foss, Catherine A; Thornton, Katherine; Nimmagadda, Sridhar; Endres, Christopher J; Uzuner, Ovsev; Seyler, Thorsten M; Ulrich, Slif D; Conway, Janet; Bettegowda, Chetan; Agrawal, Nishant; Cheong, Ian; Zhang, Xiaosong; Ladenson, Paul W; Vogelstein, Barry N; Mont, Michael A; Zhou, Shibin; Kinzler, Kenneth W; Vogelstein, Bert; Pomper, Martin G
BACKGROUND: Traditional imaging techniques for the localization and monitoring of bacterial infections, although reasonably sensitive, suffer from a lack of specificity. This is particularly true for musculoskeletal infections. Bacteria possess a thymidine kinase (TK) whose substrate specificity is distinct from that of the major human TK. The substrate specificity difference has been exploited to develop a new imaging technique that can detect the presence of viable bacteria. METHODOLOGY/PRINCIPAL FINDINGS: Eight subjects with suspected musculoskeletal infections and one healthy control were studied by a combination of [(124)I]FIAU-positron emission tomography and CT ([(124)I]FIAU-PET/CT). All patients with proven musculoskeletal infections demonstrated positive [(124)I]FIAU-PET/CT signals in the sites of concern at two hours after radiopharmaceutical administration. No adverse reactions with FIAU were observed. CONCLUSIONS/SIGNIFICANCE: [(124)I]FIAU-PET/CT is a promising new method for imaging bacterial infections.