Browsing by Author "Lopez, Giselle"

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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
Metastatic cervical paravertebral solitary fibrous tumor detected by fluorodeoxyglucose positron emission tomography-computed tomography
(Radiology Case Reports, 2018-04) Cheung, Hoiwan; Lawhn-Heath, Courtney; Lopez, Giselle; Vella, Maya; Aparici, Carina Mari
© 2018 Solitary fibrous tumors/hemangiopericytomas (SFT/HPC) are soft tissue tumors that can arise from the abdomen, pleura, head and neck, or extremities. We report an unusual case of recurrent hemangiopericytoma in a 67-year-old female presenting with a painless and palpable mass within her right posterior neck. Eight years after initial resection of the mass, a follow-up MRI showed multiple enlarging calvarial lesions. A whole body FDG-PET/CT revealed not only hypermetabolic calvarial lesions but also numerous hypermetabolic axillary node and osseous metastases. Though the majority of these soft tissue tumors exhibit benign behavior and carry a favorable prognosis, patients with these slow growing tumors are at risk for local recurrence and distant metastases which demonstrate substantial FDG avidity. Additional studies are needed to clarify the role of whole body FDG-PET/CT in the surveillance of SFT/HPC to detect recurrent or metastatic lesions.
Open Access
Supratentorial tanycytic ependymoma in an adult male: case report and review of literature.
(Case reports in oncology, 2015-01) Lopez, Giselle; McLendon, Roger E; Peters, Katherine B
Ependymomas, tumors of the ependymal cells, are very rare and usually present in the pediatric population. Furthermore, there are even rarer variants of ependymomas that can include cellular, papillary, clear cell, and tanycytic subtypes. We present a case of a supratentorial tanycytic ependymoma in an adult male and review the literature in regard to this rare primary central nervous system neoplasm.
Open Access
Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation.
(Nature, 2012-02-15) Koivunen, Peppi; Lee, Sungwoo; Duncan, Christopher G; Lopez, Giselle; Lu, Gang; Ramkissoon, Shakti; Losman, Julie A; Joensuu, Päivi; Bergmann, Ulrich; Gross, Stefan; Travins, Jeremy; Weiss, Samuel; Looper, Ryan; Ligon, Keith L; Verhaak, Roel GW; Yan, Hai; Kaelin, William G
The identification of succinate dehydrogenase (SDH), fumarate hydratase (FH) and isocitrate dehydrogenase (IDH) mutations in human cancers has rekindled the idea that altered cellular metabolism can transform cells. Inactivating SDH and FH mutations cause the accumulation of succinate and fumarate, respectively, which can inhibit 2-oxoglutarate (2-OG)-dependent enzymes, including the EGLN prolyl 4-hydroxylases that mark the hypoxia inducible factor (HIF) transcription factor for polyubiquitylation and proteasomal degradation. Inappropriate HIF activation is suspected of contributing to the pathogenesis of SDH-defective and FH-defective tumours but can suppress tumour growth in some other contexts. IDH1 and IDH2, which catalyse the interconversion of isocitrate and 2-OG, are frequently mutated in human brain tumours and leukaemias. The resulting mutants have the neomorphic ability to convert 2-OG to the (R)-enantiomer of 2-hydroxyglutarate ((R)-2HG). Here we show that (R)-2HG, but not (S)-2HG, stimulates EGLN activity, leading to diminished HIF levels, which enhances the proliferation and soft agar growth of human astrocytes. These findings define an enantiomer-specific mechanism by which the (R)-2HG that accumulates in IDH mutant brain tumours promotes transformation and provide a justification for exploring EGLN inhibition as a potential treatment strategy.