Recent Publications

Development of a novel mouse glioma model using lentiviral vectors.

Nat Med. 2009 Jan 4;

Authors: Marumoto T, Tashiro A, Friedmann-Morvinski D, Scadeng M, Soda Y, Gage FH, Verma IM

We report the development of a new method to induce glioblastoma multiforme in adult immunocompetent mice by injecting Cre-loxP-controlled lentiviral vectors expressing oncogenes. Cell type- or region-specific expression of activated forms of the oncoproteins Harvey-Ras and AKT in fewer than 60 glial fibrillary acidic protein-positive cells in the hippocampus, subventricular zone or cortex of mice heterozygous for the gene encoding the tumor suppressor Tp53 were tested. Mice developed glioblastoma multiforme when transduced either in the subventricular zone or the hippocampus. However, tumors were rarely detected when the mice were transduced in the cortex. Transplantation of brain tumor cells into naive recipient mouse brain resulted in the formation of glioblastoma multiforme-like tumors, which contained CD133(+) cells, formed tumorspheres and could differentiate into neurons and astrocytes. We suggest that the use of Cre-loxP-controlled lentiviral vectors is a novel way to generate a mouse glioblastoma multiforme model in a region- and cell type-specific manner in adult mice.

PMID: 19122659 [PubMed - as supplied by publisher]

Delivery of sodium borocaptate to glioma cells using immunoliposome conjugated with anti-EGFR antibodies by ZZ-His.

Biomaterials. 2008 Dec 31;

Authors: Feng B, Tomizawa K, Michiue H, Miyatake SI, Han XJ, Fujimura A, Seno M, Kirihata M, Matsui H

Nanoparticles are effective of delivering cargo into cells. Here, sodium borocaptate (BSH) was encapsulated in liposomes composed of nickel lipid, and anti-epidermal growth factor receptor (EGFR) antibodies were conjugated to the liposomes using the antibody affinity motif of protein A (ZZ) as an adaptor (immunoliposomes). The immunoliposomes were used to deliver BSH into EGFR-overexpressing glioma cells. Immunohistochemical analysis using an anti-BSH monoclonal antibody revealed that BSH was delivered effectively into the cells but not into EGFR-deficient glioma or primary astrocytes. In an animal model of brain tumors, both the liposomes and the BSH were only observed in the tumor. Moreover, the efficiency of (10)B's delivery into glioma cells was confirmed by inductively coupled plasma-atomic emission spectrometry (ICP-AES) both in vitro and in vivo. The results suggest that this system utilizing immunoliposomes provides an effective means of delivering (10)B into glioma cells in boron neutron capture therapy (BNCT).

PMID: 19121537 [PubMed - as supplied by publisher]

Transactivation by Runt related factor-2 of matrix metalloproteinase-13 in astrocytes.

Neurosci Lett. 2008 Dec 25;

Authors: Takarada T, Yoneda Y

We have previously shown functional expression by osteoblasts of signaling machineries required for neurotransmission in the brain. In this study, we have evaluated possible functional expression of different osseous genes in the brain. In embryonic and adult mouse brains, mRNA expression was invariably seen for the master regulator of osteoblastic differentiation Runt related factor-2 (Runx2), in addition to the partner protein core binding factor-beta and their targets such as osteopontin (OPN) and matrix metalloproteinase-13 (MMP13), but not for collagen-I or osteocalcin. In pluripotent P19 progenitor cells, Runx2 mRNA expression was drastically increased along with mRNA expression of an astrocytic marker, but not with neuronal marker mRNA expression. Both mRNA and corresponding protein were detected for Runx2 in cultured rat neocortical astrocytes and astrocytic C6 glioma cells. In C6 glioma cells, transient overexpression of Runx2 significantly increased mRNA expression of MMP13, but not of OPN. Moreover, transient overexpression of Runx2 significantly increased luciferase activity in C6 glioma cells transfected with the reporter plasmid linked to a wild-type Runx2 binding element in the MMP13 promoter, but not in cells with a mutated element. These results suggest that Runx2 signal input may lead to transactivation of MMP13 gene without affecting OPN expression in astrocytes.

PMID: 19121369 [PubMed - as supplied by publisher]

MMSET is overexpressed in cancers: Link with tumor aggressiveness.

Biochem Biophys Res Commun. 2008 Dec 30;

Authors: Kassambara A, Klein B, Moreaux J

MMSET is expressed ubiquitously in early development and its deletion is associated with the malformation syndrome called Wolf-Hirschhorn syndrome. It is involved in the t(4;14) (p16;q32) chromosomal translocation, which is the second most common translocation in multiple myeloma (MM) and is associated with the worst prognosis. MMSET expression has been shown to promote cellular adhesion, clonogenic growth and tumorigenicity in multiple myeloma. MMSET expression has been recently shown to increase with ascending tumor proliferation activity in glioblastoma multiforme. These data demonstrate that MMSET could be implicated in tumor emergence and/or progression. Therefore, we compared the expression of MMSET in 40 human tumor types - brain, epithelial, lymphoid - to that of their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database. We found significant overexpression of MMSET in 15 cancers compared to their normal counterparts. Furthermore MMSET is associated with tumor aggressiveness or prognosis in many types of these aforementioned cancers. Taken together, these data suggest that MMSET potentially acts as a pathogenic agent in many cancers. The identification of the targets of MMSET and their role in cell growth and survival will be key to understand how MMSET is associated with tumor development.

PMID: 19121287 [PubMed - as supplied by publisher]

Breaching the barrier.

Nat Biotechnol. 2008 Nov;26(11):1213-5

Authors: Dove A

PMID: 18997754 [PubMed - indexed for MEDLINE]

[Brain neoplasm surgery with acupuncture anesthesia and intravenous anesthesia]

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2008 Mar;28(3):279-80

Authors: Li J, Guo X, Yan HC, et al

PMID: 18958936 [PubMed - indexed for MEDLINE]

Cellular localization of metabotropic glutamate receptors in cortical tubers and subependymal giant cell tumors of tuberous sclerosis complex.

Neuroscience. 2008 Sep 22;156(1):203-15

Authors: Boer K, Troost D, Timmermans W, Gorter JA, Spliet WG, Nellist M, Jansen F, Aronica E

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder associated with cortical malformations (cortical tubers) and the development of glial tumors (subependymal giant-cell tumors, SGCTs). Expression of metabotropic glutamate receptor (mGluR) subtypes is developmentally regulated and several studies suggest an involvement of mGluR-mediated glutamate signaling in the regulation of proliferation and survival of neural stem-progenitor cells, as well as in the control of tumor growth. In the present study, we have investigated the expression and cell-specific distribution of group I (mGluR1, mGluR5), group II (mGluR2/3) and group III (mGluR4 and mGluR8) mGluR subtypes in human TSC specimens of both cortical tubers and SGCTs, using immunocytochemistry. Strong group I mGluR immunoreactivity (IR) was observed in the large majority of TSC specimens in dysplastic neurons and in giant cells within cortical tubers, as well as in tumor cells within SGCTs. In particular mGluR5 appeared to be most frequently expressed, whereas mGluR1alpha was detected in a subpopulation of neurons and giant cells. Cells expressing mGluR1alpha and mGluR5, demonstrate IR for phospho-S6 ribosomal protein (PS6), which is a marker of the mammalian target of rapamycin (mTOR) pathway activation. Group II and particularly group III mGluR IR was less frequently observed than group I mGluRs in dysplastic neurons and giant cells of tubers and tumor cells of SGCTs. Reactive astrocytes were mainly stained with mGluR5 and mGluR2/3. These findings expand our knowledge concerning the cellular phenotype in cortical tubers and in SGCTs and highlight the role of group I mGluRs as important mediators of glutamate signaling in TSC brain lesions. Individual mGluR subtypes may represent potential pharmacological targets for the treatment of the neurological manifestations associated with TSC brain lesions.

PMID: 18706978 [PubMed - indexed for MEDLINE]

Infantile gliosarcoma.

Arq Neuropsiquiatr. 2008 Mar;66(1):88-9

Authors: Melo JR, Souza AL, Reis RC, Almeida MA

PMID: 18392424 [PubMed - indexed for MEDLINE]

Primary diffuse leptomeningeal gliomatosis.

Arq Neuropsiquiatr. 2008 Mar;66(1):85-7

Authors: Gonçalves AL, Masruha MR, Carrete Jr H, Stávale JN, Silva NS, Vilanova LC

PMID: 18392423 [PubMed - indexed for MEDLINE]

Disseminated intravascular coagulation in a patient undergoing removal of metastatic brain tumor.

J Korean Neurosurg Soc. 2008 Nov;44(5):341-4

Authors: Eom KS, Kim JM, Kim TY

The authors present a case of 68-year-old woman who underwent resection of a metastatic adenocarcinoma in the left parietooccipital area. The intraoperative course was uneventful; however, after closure of the scalp incision, increased bleeding from the suture line was noted. A computerized tomography scan that was performed immediately after operation revealed acute epidural hemorrhage with mass effect under the bone flap. The patient developed disseminated intravascular coagulation and immediate re-exploration was performed. This patient was successfully treated owing to early recognition of the condition and immediate treatment with transfusion. Neurosurgeons should be alert that hypercoagulabe state is common in cancer patients and consumptive coagulopathy can occur after resection of metastatic brain tumor.

PMID: 19119473 [PubMed - in process]

Brain cancer. A viral link to glioblastoma?

Science. 2009 Jan 2;323(5910):30-1

Authors: Miller G

PMID: 19119195 [PubMed - in process]

Lipomatous supratentorial primitive neuroectodermal tumor with glioblastomatous differentiation.

Ann Diagn Pathol. 2009 Feb;13(1):36-40

Authors: Prayson RA

Cases of cerebral neuroblastoma or supratentorial primitive neuroectodermal tumor with malignant gliomatous components are relatively uncommon. Less frequent is the combination of these 2 elements with a mesenchymal component. This is a case report of a lipomatous supratentorial primitive neuroectodermal tumor with glioblastomatous differentiation occurring in a 48-year-old woman. She presented with headaches and confusion. A right parietal lobe mass was excised and subsequently recurred, requiring additional surgery 10 months later. The patient died 13 months after initial surgery. Histologic findings showed a proliferation of small rounded synaptophysin-positive neural cells consistent with neuroblastoma. These cells were arranged against a benign lipomatous background. The second resection consisted primarily of glioblastomatous-like tissue with intermixed lipomatous component. The glioblastoma component was marked by prominent cellularity, moderate nuclear pleomorphism, readily identifiable mitotic activity, vascular proliferative changes, and necrosis. The glioblastomatous component of the tumor demonstrated glial fibrillary acidic protein immunoreactivity. A Ki-67 labeling index of 18.9% was noted in the initial resection. The literature on similar-appearing lesions is reviewed.

PMID: 19118780 [PubMed - in process]

Angiogenesis, hypoxia and VEGF expression during tumour growth in a human xenograft tumour model.

Microvasc Res. 2008 Dec 7;

Authors: Hendriksen EM, Span PN, Schuuring J, Peters JP, Sweep FC, van der Kogel AJ, Bussink J

Tumour growth and spread of tumour cells require angiogenesis. Incipient angiogenesis is not induced by tumour cell hypoxia but probably by proangiogenic factors. During growth, tumours depend on a further induction of vascular development for adequate oxygen and nutrient supply. If the oxygen supply is insufficient, the resulting hypoxia stimulates angiogenesis through upregulation of HIF-1alpha and VEGF. VEGF upregulation is associated with a poor response to treatment and poor prognosis. We investigated angiogenesis during tumour growth in relation to hypoxia and VEGF-expression. Tumours from the human glioblastoma multiforme tumour line E106 were transplanted in athymic mice. Tumours were harvested at different time points; the first group at 2 days after transplantation at a size of <1 mm and the other groups at a mean size of 2, 4, 6, 8 and 10 mm. VEGF was present early in the onset of angiogenesis independent of HIF-1alpha. During tumour growth VEGF increased from 0.94 to 7.27 ng/mg assessed by ELISA. There was increasing intratumoural heterogeneity in the architecture of the tumours and even in the largest tumours small well oxygenated areas were detected resembling the relatively well organized architecture of the smallest tumours. The observation that tumour vasculature develops through HIF-1alpha dependent and HIF-1alpha independent pathways and the presence of both vascular patterns in the larger tumours, indicates that anti-angiogenic therapy should be directed towards both pathways.

PMID: 19118564 [PubMed - as supplied by publisher]

Phase II Study of Protracted Daily Temozolomide for Low-Grade Gliomas in Adults.

Clin Cancer Res. 2009 Jan 1;15(1):330-337

Authors: Kesari S, Schiff D, Drappatz J, Lafrankie D, Doherty L, Macklin EA, Muzikansky A, Santagata S, Ligon KL, Norden AD, Ciampa A, Bradshaw J, Levy B, Radakovic G, Ramakrishna N, Black PM, Wen PY

PURPOSE: Resistance to temozolomide chemotherapy is partly mediated by O(6)-methylguanine-DNA methlytransferase (MGMT). Protracted treatment with temozolomide potentially overcomes MGMT resistance and improves outcome. We conducted a phase II study of protracted daily temozolomide in adults with low-grade gliomas. EXPERIMENTAL DESIGN: Patients with newly diagnosed oligodendroglioma or oligoastrocytoma with a MIB-1 index of >5% or recurrent low-grade gliomas received temozolomide (75 mg/m(2)/day in 11-week cycles of 7 weeks on/4 weeks off). Treatment continued for a total of six cycles or until tumor progression or unacceptable toxicity. Primary end point was best overall response rate; secondary end points were progression-free survival, overall survival, and toxicity. We correlated response with MGMT promoter methylation and chromosome 1p/19q deletion status. RESULTS: Forty-four patients were treated (14 female, 30 male) with a median follow-up of 39.4 months. Median age was 43 years (range, 20-68 years) and median Karnofsky performance status was 90 (range, 70-100). The regimen was well tolerated. No patients had a complete response (0%), 9 had partial response (20%), 33 had stable disease (75%), and 2 had progressive disease (5%). A total of 21 patients eventually progressed with an overall median progression-free survival of 38 months. Patients with methylated MGMT promoter had a longer overall survival (P = 0.008). Deletion of either 1p or 19q chromosomes also predicted longer overall survival (hazard ratio, 0.17; 95% confidence interval, 0.03-0.93; log-rank P = 0.02). CONCLUSIONS: A protracted course of daily temozolomide is a well-tolerated regimen and seems to produce effective tumor control. This compares favorably with historical data on the standard 5-day temozolomide regimen.

PMID: 19118062 [PubMed - as supplied by publisher]

Reoxygenation of hypoxic glioblastoma multiforme cells potentiates the killing effect of an interleukin-13-based cytotoxin.

Clin Cancer Res. 2009 Jan 1;15(1):160-8

Authors: Liu TF, Cai J, Gibo DM, Debinski W

PURPOSE: Hypoxia is a cause for resistance to cancer therapies. Molecularly targeted recombinant cytotoxins have shown clinical efficacy in the treatment of patients with primary brain tumors, glioblastoma multiforme, but it is not known whether hypoxia influences their antitumor effect. EXPERIMENTAL DESIGN: We have exposed glioblastoma multiforme cells, such as U-251 MG, U-373 MG, SNB-19, and A-172 MG, to either anoxia or hypoxia and then reoxygenated them while treating with an interleukin (IL)-13-based diphtheria toxin (DT)-containing cytotoxin, DT-IL13QM. We measured the levels of immunoreactive IL-13Ralpha2, a receptor that mediates IL-13-cytotoxin cell killing, and the levels of active form of furin, a protease that activates the bacterial toxin portion in a cytotoxin. RESULTS: We found that anoxia/hypoxia significantly alters the responsiveness of glioblastoma multiforme cells to DT-IL13QM. Interestingly, bringing these cells back to normoxia caused them to become even more susceptible to the cytotoxin than the cells maintained under normoxia. Anoxia/hypoxia caused a highly prominent decrease in the immunoreactive levels of both IL-13R and active forms of furin, and reoxygenation not only restored their levels but also became higher than that in normoxic glioblastoma multiforme cells. CONCLUSIONS: Our results show that a recombinant cytotoxin directed against glioblastoma multiforme cells kills these cells much less efficiently under anoxic/hypoxic conditions. The reoxygenation brings unexpected additional benefit of making glioblastoma multiforme cells even more responsive to the killing effect of a cytotoxin.

PMID: 19118043 [PubMed - in process]

A new model for prediction of drug distribution in tumor and normal tissues: pharmacokinetics of temozolomide in glioma patients.

Cancer Res. 2009 Jan 1;69(1):120-7

Authors: Rosso L, Brock CS, Gallo JM, Saleem A, Price PM, Turkheimer FE, Aboagye EO

Difficulties in direct measurement of drug concentrations in human tissues have hampered the understanding of drug accumulation in tumors and normal tissues. We propose a new system analysis modeling approach to characterize drug distribution in tissues based on human positron emission tomography (PET) data. The PET system analysis method was applied to temozolomide, an important alkylating agent used in the treatment of brain tumors, as part of standard temozolomide treatment regimens in patients. The system analysis technique, embodied in the convolution integral, generated an impulse response function that, when convolved with temozolomide plasma concentration input functions, yielded predicted normal brain and brain tumor temozolomide concentration profiles for different temozolomide dosing regimens (75-200 mg/m(2)/d). Predicted peak concentrations of temozolomide ranged from 2.9 to 6.7 microg/mL in human glioma tumors and from 1.8 to 3.7 microg/mL in normal brain, with the total drug exposure, as indicated by the tissue/plasma area under the curve ratio, being about 1.3 in tumor compared with 0.9 in normal brain. The higher temozolomide exposures in brain tumor relative to normal brain were attributed to breakdown of the blood-brain barrier and possibly secondary to increased intratumoral angiogenesis. Overall, the method is considered a robust tool to analyze and predict tissue drug concentrations to help select the most rational dosing schedules.

PMID: 19117994 [PubMed - in process]

Early clinical and neuroradiological worsening after radiotherapy and concomitant temozolomide in patients with glioblastoma: Tumour progression or radionecrosis?

Clin Neurol Neurosurg. 2008 Dec 29;

Authors: Peca C, Pacelli R, Elefante A, Del Basso De Caro ML, Vergara P, Mariniello G, Giamundo A, Maiuri F

OBJECTIVES: This study investigates the diagnosis and management of patients with resected brain glioblastomas who presented early clinical and neuroradiological worsening after the completion of the Stupp protocol. Its aim is to discuss the occurrence of early radionecrosis. METHODS: Fifty patients with brain glioblastoma treated by surgical resection and Stupp protocol were reviewed; 15 among them (30%) had early clinical and neuroradiological worsening at the 6-month follow-up. The MR spectroscopy and surgical findings of these patients are reviewed. RESULTS: MR spectroscopy was in favour of tumour recurrence in 14 among 15 patients and showed radionecrosis in one. Among 10 patients who were reoperated on, 7 had histologically verified tumour recurrence or regrowth, whereas in 3 histopathology showed necrosis without evidence of tumour. The 7 patients with tumour progression had prevalence of focal neuroradiological signs (6/7) and a survival of 7.5-12 months (median survival 10 months). The 4 patients with early radionecrosis (including one patient who was not reoperated on) had clinical worsening with mental deterioration, confusion and ataxia, and MR spectroscopy positive for tumour recurrence in 3. Three were alive 24-30 months after the end of the radiotherapy, whereas one died at 40 months. CONCLUSION: Early radionecrosis after the Stupp protocol is not a rare event due to the radiosensitization effect of temozolomide. This phenomenon may predict a durable response to radiotherapy. MR spectroscopy may simulate tumour recurrence. A correct diagnosis is necessary to avoid useless reoperations and incorrect withdrawal of temozolomide.

PMID: 19117668 [PubMed - as supplied by publisher]

Alterations in lipid peroxidation and antioxidant status in different types of intracranial tumors within their relative peritumoral tissues.

Clin Neurol Neurosurg. 2008 Dec 29;

Authors: Zengin E, Atukeren P, Kokoglu E, Gumustas MK, Zengin U

OBJECTIVES: Elevated levels of lipid peroxidation and changes in the concentration of enzymatic and non-enzymatic antioxidant systems have been reported in various cancers, but there are very few reports available of lipid peroxidation due to oxidative stress in patients with intracranial neoplasms. The purpose of this study was to assess alterations in lipid peroxidation and antioxidant status in different types of tumors and to compare the results with their relative peritumoral tissues and compare the oxidative status in different grades of tumors. PATIENTS AND METHODS: We investigated the extent of oxidative stress and the levels of antioxidants in 16 astrocytomas and 38 other different types intracranial tumors comparing the results with their corresponding peritumoral tissues and comparing the levels in between low-grade and high-grade tumors. The extent of lipid peroxidation as evidenced by the formation of thiobarbituric acid-reacting substances (TBARS), as well as the status of the antioxidant systems such as superoxide dismutase (SOD), glutathione reductase (GR) and reduced glutathione (GSH) in tumor tissues and adjacent peritumoral tissues was estimated. The tumoral tissues were also compared as to their degrees of malignancy. RESULTS: According to our results lipid peroxidation in brain tumor tissues was enhanced compared to the corresponding adjacent peritumoral tissues. This was accompanied by a significant tumoral decrease in both enzymatic and non-enzymatic antioxidants. The low levels of antioxidants in tumor tissues, might be related to an increased use of antioxidant systems to scavenge lipid peroxides. Also a striking elevation in TBARS levels, and decrease in SOD activity and GSH levels were seen in high-grade tumors when compared with low grades. CONCLUSION: These findings emphasize a consistent difference in the level of antioxidants between the tumoral sample and its corresponding peritumoral tissue, independently of the tumoral type, and the most pivotal action would seem to minimise exposure to endogenous and exogenous sources of oxidative stress.

PMID: 19117666 [PubMed - as supplied by publisher]

Dynamic Biochemical Information Recovery in Spontaneous Human Seminal Fluid Reactions via (1)H NMR Kinetic Statistical Total Correlation Spectroscopy.

Anal Chem. 2009 Jan 1;81(1):288-295

Authors: Maher AD, Cloarec O, Patki P, Craggs M, Holmes E, Lindon JC, Nicholson JK

Human seminal fluid (HSF) is a complex mixture of reacting glandular metabolite and protein secretions that provides critical support functions in fertilization. We have employed 600-MHz (1)H NMR spectroscopy to compare and contrast the temporal biochemical and biophysical changes in HSF from infertile men with spinal cord injury compared to age-matched controls. We have developed new approaches to data analysis and visualization to facilitate the interpretation of the results, including the first application of the recently published K-STOCSY concept to a biofluid, enhancing the extraction of information on biochemically related metabolites and assignment of resonances from the major seminal protein, semenogelin. Principal components analysis was also applied to evaluate the extent to which macromolecules influence the overall variation in the metabolic data set. The K-STOCSY concept was utilized further to determine the relationships between reaction rates and metabolite levels, revealing that choline, N-acetylglucosamine, and uridine are associated with higher peptidase activity. The novel approach adopted here has the potential to capture dynamic information in any complex mixture of reacting chemicals including other biofluids or cell extracts.

PMID: 19117456 [PubMed - as supplied by publisher]

IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors.

Hum Mutat. 2008 Dec 31;

Authors: Bleeker FE, Lamba S, Leenstra S, Troost D, Hulsebos T, Vandertop WP, Frattini M, Molinari F, Knowles M, Cerrato A, Rodolfo M, Scarpa A, Felicioni L, Buttitta F, Malatesta S, Marchetti A, Bardelli A

Systematic sequence profiling of the Glioblastoma Multiforme (GBM) genome has recently led to the identification of somatic mutations in the isocitrate dehydrogenase 1 (IDH1) gene. Interestingly, only the evolutionarily conserved residue R132 located in the substrate binding site of IDH1 was found mutated in GBM. At present, the occurrence and the relevance of p.R132 (IDH1(R132)) variants in tumors other than GBMs is largely unknown. We searched for mutations at position R132 of the IDH1 gene in a panel of 672 tumor samples. These included high-grade glioma, gastrointestinal stromal tumors (GIST), melanoma, bladder, breast, colorectal, lung, ovarian, pancreas, prostate, and thyroid carcinoma specimens. In addition, we assessed a panel of 84 cell lines from different tumor lineages. Somatic mutations affecting the IDH1(R132) residue were detected in 20% (23 of 113) high-grade glioma samples. In addition to the previously reported p.R132H and p.R132S alleles, we identified three novel somatic mutations (p.R132C, p.R132G, and p.R132L) affecting residue IDH1(R132) in GBM. Strikingly, no IDH1 mutations were detected in the other tumor types. These data indicate that cancer mutations affecting IDH1(R132) are tissue-specific, and suggest that it plays a unique role in the development of high-grade gliomas. Hum Mutat 30, 1-5, 2009. (c) 2008 Wiley-Liss, Inc.

PMID: 19117336 [PubMed - as supplied by publisher]