Biased usage of T cell receptor ß-chain variable region genes of Wilms' tumor gene (WT1)-specific CD8+ T cells in patients with solid tumors and healthy donors.

Wilms' tumor gene 1 (WT1) protein is a promising tumor-associated antigen. In patients with WT1-expressing malignancies, WT1-specific CTLs are spontaneously induced as a result of an immune response to the WT1 protein. In the present study, we performed single cell-level comparative analysis of T cell receptor ß-chain variable region (TCR-BV) gene families of a total of 750 spontaneously induced WT1(126) peptide (amino acids 126-134, WT1(126))-specific CTLs in both HLA-A*0201(+) patients with solid tumors and healthy donors (HDs). This is the first report of direct usage analysis of 24 kinds of TCR-BV gene families of WT1(126)-specific CTLs at the single cell level. Usage analysis with single-cell RT-PCR of TCR-BV gene families of individual FACS-sorted WT1(126) tetramer(+) CD8(+) T cells showed, for the first time, that: (i) BVs 3, 6, 7, 20, 27, and 28 were commonly biased in patients and HDs; (ii) BVs 2, 11, and 15 were biased only in patients; and (iii) BVs 4, 5, 9, and 19 were biased only in HDs. However, statistical analysis of similarity of individual usage frequencies of 24 kinds of TCR-BV gene families between patients and HDs indicated that the usage frequencies of TCR-BV gene families in patients reflected those in HDs. These results should provide us with a novel insight for a better understanding of WT1-specific immune responses.

Immunohistological profiling by B-cell differentiation status of primary central nervous system lymphoma treated by high-dose methotrexate chemotherapy.

Primary central nervous system lymphoma (PCNSL) remains a devastating disease with poor prognosis, despite the improvement offered by methotrexate (MTX)-based chemotherapy. Several studies have attempted to identify biomarkers predictive of prognosis, which are expected to be both clinically useful and biologically important for understanding PCNSL. The present study attempts to classify human immunodeficiency virus (HIV)-unrelated PCNSL patients treated with radiation combined with rapid high-dose MTX chemotherapy according to B-cell differentiation status, and retrospectively examines the prognostic impact. Initial response to MTX was a strong predictor of favorable prognosis in terms of both progression-free survival (PFS) and overall survival (OS). Thirteen out of 29 cases were CD10(-)/BCL-6(+)/MUM-1(+), being more frequent compared with systemic peripheral nodal lymphoma. Although post-germinal-center B-cell-originating PCNSLs (CD10(-)/BCL-6(-)/MUM-1(+)) showed a trend towards better response to MTX and progression-free survival than did germinal-center-related B-cell-originating PCNSLs (CD10(+) OR CD10(-)/BCL-6(+)/MUM-1(+)), the difference was only marginal (P = 0.04 Gehan-Breslow-Wilcoxon, P = 0.17 log-rank). Our results imply that different B-cell stages in PCNSL have significant relevance in terms of biological behavior. However, clinical use as a prognostic marker requires further investigation.

Serial volumetric assessment of the natural history and growth pattern of incidentally discovered meningiomas.

OBJECT: Due to advances in neuroimaging and the increasing use of imaging to screen for brain disease ("brain checkups"), meningiomas are now often detected as an incidental finding. The natural history of these asymptomatic meningiomas remains unclear, however. In this study, the authors investigated the natural history and growth pattern of incidentally detected meningiomas using serial volumetric assessment and regression analysis. METHODS: In 70 patients with incidentally discovered meningiomas who underwent follow-up for longer than 1 year, tumor volumes were calculated volumetrically at each follow-up visit, and tumor growth was determined. In patients with tumor growth, regression analysis was performed to determine the pattern of growth. RESULTS: Forty-four tumors exhibited growth and 26 did not. In a regression analysis, 16 of the tumors that grew followed an exponential growth pattern and 15 exhibited linear growth patterns. The presence of calcification was the only imaging characteristic that significantly distinguished the group with tumor growth from that without, although no radiological characteristics significantly distinguished the exponential growth group from the linear growth group. Two patients with obvious tumor growth underwent surgical removal and the pathological specimens extracted showed a high proliferative potential. CONCLUSIONS: The authors found that incidentally discovered meningiomas did not always follow an exponential growth pattern but often exhibited more complex patterns of growth. Serial monitoring of tumor volumes and regression analysis may reveal the growth pattern of incidental meningiomas and provide information useful for determining treatment strategy.

Phase II clinical trial of Wilms tumor 1 peptide vaccination for patients with recurrent glioblastoma multiforme.

OBJECT: The object of this study was to investigate the safety and clinical responses of immunotherapy targeting the WT1 (Wilms tumor 1) gene product in patients with recurrent glioblastoma multiforme (GBM). METHODS: Twenty-one patients with WT1/HLA-A*2402-positive recurrent GBM were included in a Phase II clinical study of WT1 vaccine therapy. In all patients, the tumors were resistant to standard therapy. Patients received intra-dermal injections of an HLA-A*2402-restricted, modified 9-mer WT1 peptide every week for 12 weeks. Tumor size, which was obtained by measuring the contrast-enhanced area on magnetic resonance images, was determined every 4 weeks. The responses were analyzed according to Response Evaluation Criteria in Solid Tumors (RECIST) 12 weeks after the initial vaccination. Patients who achieved an effective response continued to be vaccinated until tumor progression occurred. Progression-free survival and overall survival after initial WT1 treatment were estimated. RESULTS: The protocol was well tolerated; only local erythema occurred at the WT1 vaccine injection site. The clinical responses were as follows: partial response in 2 patients, stable disease in 10 patients, and progressive disease in 9 patients. No patient had a complete response. The overall response rate (cases with complete or partial response) was 9.5%, and the disease control rate (cases with complete or partial response as well as those in which disease was stable) was 57.1%. The median progression-free survival (PFS) period was 20.0 weeks, and the 6-month (26-week) PFS rate was 33.3%. CONCLUSIONS: Although a small uncontrolled nonrandomized trial, this study showed that WT1 vaccine therapy for patients with WT1/HLA-A*2402-positive recurrent GBM was safe and produced a clinical response. Based on these results, further clinical studies of WT1 vaccine therapy in patients with malignant glioma are warranted.

Crossed cerebellar diaschisis: a positron emission tomography study with L-[methyl-11C]methionine and 2-deoxy-2-[18F]fluoro-D-glucose.

OBJECTIVE: Crossed cerebellar diaschisis (CCD) is defined as a depression of blood flow and oxidative metabolism of glucose in the cerebellum contralateral to a supratentorial brain lesion, as detected with positron emission tomography (PET) and single photon emission computed tomography. We examined whether L-[methyl-11C]methionine (MET) uptake is affected in CCD. METHODS: In 12 patients with a unilateral supratentorial brain tumor, we evaluated the uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and MET in the cerebellar hemispheres by means of PET. Asymmetry index (AI) was defined as a difference in the average count between the ipsilateral and contralateral cerebellar hemispheres divided by the average count in both cerebellar hemispheres. Patients with AI of FDG PET more than 0.1 and those with AI equal to 0.1 or less than 0.1 were classified as CCD-positive and CCD-negative, respectively. RESULTS: Six patients were CCD-positive and others were CCD-negative in the FDG PET study. Between CCD-positive and CCD-negative patients, mean AI of MET was not significantly different (0.017 +/- 0.023 and 0.014 +/- 0.039, respectively). CONCLUSIONS: Different from glucose metabolism, cerebellar MET uptake was not affected in CCD. The present study may indicate that cerebellar MET uptake is independent of suppression of cerebellar neuronal activity.

Expression of WT1 protein and correlation with cellular proliferation in glial tumors.

The expression of Wilms' tumor gene WT1 protein was investigated immunohistochemically in 73 glial tumors, including 60 astrocytic tumors, eight oligodendroglial tumors, and five ependymal tumors. WT1 protein was detected in 70 of the 73 glial tumors (95.9%) examined. Almost all glioblastomas, anaplastic astrocytomas, anaplastic ependymomas, and anaplastic oligodendrogliomas expressed high levels of WT1 protein. A significant (p < 0.001) correlation was found between WT1 protein expression and MIB-1 staining index. Histological examination found that WT1 protein was strongly expressed in the anaplastic portions and areas with perivascular proliferation and high cellularity, implying that WT1 gene might be important in glial tumor cell proliferation. WT1 gene is overexpressed in various types of solid tumors and WT1 protein is a target antigen for cancer immunotherapy. This study indicates that many malignant glial tumors are good candidates for cancer immunotherapy targeting WT1 protein and that WT1 protein expression could be used as a proliferation marker in glial tumors.

Detection of genetic and chromosomal aberrations in medulloblastomas and primitive neuroectodermal tumors with DNA microarrays.

Medulloblastoma (MB) is the most frequent infratentorial malignant brain tumor in children. In contrast, primitive neuroectodermal tumor (PNET) is defined as a supratentorial malignant tumor generated from the cerebral hemisphere. These tumors have considerable histological overlap but have different clinical outcomes including overall survival period, recurrence rate, and chemosensitivity. We investigated the amplification and/or deletion of genes and the chromosomal gain and/or loss in 10 MBs and 3 PNETs with a genomic DNA microarray system. Genes that are frequently amplified in these both these tumors include MSH2, N-myc, AKT3, and EGFR. Amplifications of SNRPN, MYB, and PTEN are observed only in MB. The genes associated with Wnt/APC and Shh/PTCH pathways also have some aberrations. Common chromosomal aberrations include gains at 17q and 7q and losses at 17p. Minor chromosomal losses were also detected at 1p, 8p + q, 11p, 10p + q, 13q, 16q, and Xp + q in MB. SPNETs tend to contain fewer chromosomal and genetic abnormalities than MBs. In conclusion, there are gene expression and chromosomal differences between MBs and SPNETs. These differences may correlate with the prognosis.

Scoring radiologic characteristics to predict proliferative potential in meningiomas.

We investigated the feasibility of using radiologic characteristics to predict the proliferative potential in meningiomas. Our statistical analysis revealed that the presence of peritumoral edema, an ambiguous brain-tumor border, and irregular tumor shape were significantly correlated with a higher MIB-1 staining index (SI) value. We developed the following scoring system for specific features in each tumor: peritumoral edema (tumor with edema = 1, tumor without edema = 0); brain-tumor border (tumor with any ambiguous border = 1, tumor circumscribed by a distinct rim = 0); and tumor shape (tumor with irregular shape = 1, tumor with smooth shape = 0). Using Spearman's correlation coefficient analysis, we found a significant correlation (P < 0.005) between total score calculated for each patient and SI value. Our findings suggest that the proliferative potential of meningiomas can be predicted using a less invasive preoperative examination focusing on the presence of peritumoral edema, ambiguous brain-tumor border, and irregular tumor shape.

Giant cell type of primary intracranial malignant fibrous histiocytoma: a case report.

The primary intracranial giant cell type of malignant fibrous histiocytoma (GC-MFH) is rare, and the resemblance to meningioma causes diagnostic confusion. Discrimination from meningioma bears important therapeutic and prognostic implications. We report one such case in which an extracranial malignant neoplasm was seen after the initial diagnosis and treatment. A 62-year-old woman presented with history of seizure. MRI revealed a huge right frontotemporal, homogeneously enhanced extraaxial lesion with significant mass effect. The main vascular supply was the middle meningeal artery. Workup for lesions elsewhere was negative. Gross total resection including dural attachment was achieved. The histopathological features were consistent with the diagnosis of GC-MFH. Immunohistochemistry disclosed varied reactivity profiles in tumor component cells: the spindle-shaped cells possessed features of mesenchymal and hematopoietic lineage, the histiocytic cells those of mesenchymal and epithelial cells, and the osteoclast-like multinucleated giant cells those of monocyte/macrophage and epithelial cells. Proliferative activity was absent in giant cells. Local irradiation of 60 Gy (linac) was performed. The patient did well for 10 months, and follow-up MRI showed no evidence of tumor recurrence. Subsequently, she developed ascites and died 3 months later as a consequence of end-stage adenocarcinoma (ovary) with peritoneal dissemination. There is no established treatment protocol for primary intracranial MFH. Although gross total resection and local irradiation were effective in the short-term control of local relapse in the present case, occurrence of extracranial neoplasm was fatal. Close follow-up aimed at early detection of local recurrence and distant metastases, as well as extracranial malignancy, remains important.

Skull metastasis from papillary thyroid carcinoma accompanied by neurofibromatosis type 1 and pheochromocytoma: report of a case.

We report here a 74-year-old woman with a skull metastasis from papillary thyroid carcinoma (PTC). In her medical history, she was diagnosed with neurofibromatosis type 1 (NF1) at age 28 years, and she underwent thyroidectomy for PTC at age 52 years and adrenectomy for pheochromocytoma (PC) at age 58 years. She was admitted to our hospital with an increased mass in the forehead. Head computed tomography (CT) showed an expansive, osteolytic, and solid tumor extending from the dura mater into the subcutis, destroying part of the frontal bone. Head magnetic resonance imaging (MRI) revealed that the tumor was chiefly extradural but partially invaded the dura mater. Cerebral angiography showed that the tumor was fed from a branch of the external carotid artery. She underwent surgery, and histological examination revealed that the skull tumor was a metastasis from PTC, indicating that skull metastasis occurred 23 years after curative surgery for PTC. The patient also underwent adjuvant radioiodine therapy. As little is known about skull metastases from PTC, we discuss its characteristics and the extremely rare combined occurrence of PC and PTC in an NF1 patient.

Skull metastases from atypical pulmonary carcinoid tumor in a 19-year-old man.

A 19-year-old man presented with a rare skull metastasis from atypical pulmonary carcinoid tumor (APCT) manifesting as headache, diplopia, and cough. Head magnetic resonance imaging showed a skull base tumor extending from the posterior clinoid process to the clivus, and calvarial tumors in the right temporal and occipital bones. Chest and abdominal computed tomography showed a round tumor, 4 cm in diameter, in the lower lobe of the right lung and multiple small tumors in the liver. Surgery for the calvarial tumor in the right temporal bone was performed on June 27, 2003. The histological diagnosis was skull metastasis of neuroendocrine tumor. Gamma knife radiosurgery was performed for the residual skull metastases. Partial resection of the right lower lobe was performed for the lung tumor on August 22, 2003. The histological diagnosis was atypical carcinoid tumor. Subsequent adjuvant systematic chemotherapy was performed. The patient died of progression of the tumors in the lung and liver on April 19, 2004. We must consider APCT in the differential diagnosis of pulmonary tumors in adolescents, and perform follow-up observation or treatment, including surgery, if APCT is suspected.

[Efficacy and safety of monotherapy with temozolomide in patients with anaplastic astrocytoma at first relapse--a phase II clinical study].

The efficacy and safety of temozolomide were evaluated in 32 patients with anaplastic astrocytoma at first relapse. Temozolomide was administered orally once daily for the first five days of a 28-day cycle, at a dose of 150 or 200 mg/m(2)/day. The response rate determined by independent central review of MRI was 34% (95% confidence interval: 18.6%-53.2%), with 3 complete response and 8 partial response. The rate of "no change or better" was 91% (95% confidence interval: 75.0%-98.0%). Progression-free survival (PFS) at 6 months was 40.6%, and the median PFS was 4.1 months. The incidence of constipation (50%) and nausea (25%) was high,but these events were all mild or moderate in severity except in one subject with constipation,and could be managed with standard laxatives and antiemetics. The main laboratory test abnormalities (total incidence and incidence of grade 3/4 change) were lymphocytopenia (50%, 25%), neutropenia (47%, 6%), leukopenia (38%, 3%), thrombocytopenia (31%, 9%), and increased GPT (25%, 3%). Temozolomide was shown to have good efficacy and tolerability in patients with anaplastic astrocytoma at first relapse.

Combination gene therapy for glioblastoma involving herpes simplex virus vector-mediated codelivery of mutant IkappaBalpha and HSV thymidine kinase.

To improve the effectiveness of herpes simplex virus (HSV) thymidine kinase/ganciclovir (HSV-tk/GCV) suicide gene therapy, the replication-defective HSV vector TOIkappaB expressing both HSV-TK and a mutant form of the NF-kappaB inhibitor IkappaBalpha (IkappaBalphaM) was developed. TOIkappaB was constructed by recombining the IkappaBalphaM gene into the U(L)41 locus of a replication-defective lacZ expression vector, TOZ.1. Expression of IkappaBalphaM was confirmed by Western blotting, and the ability of the mutant protein to inhibit NF-kappaB nuclear translocation was examined by electrophoretic mobility shift assay. In human glioblastoma U-87MG cells, the p50/p50 dimer of NF-kappaB was already translocated to the nucleus without receptor-dependent signaling by TNF-alpha. Following infection with TOIkappaB, nuclear translocation of NF-kappaB in U-87MG cells was significantly inhibited and caspase-3 activity increased compared with TOZ.1-infected cells. The cytotoxicity of TOIkappaB for U-87MG cells was investigated by colorimetric MTT assay. At an MOI of 3, TOIkappaB infection killed 85% of the cells compared to 20% killed by TOZ.1 infection. In the presence of GCV, these numbers increased to 95-100% for TOIkappaB and 80-85% for TOZ.1. TOIkappaB neurotoxicity measured on cultured murine neurons was relatively low and similar to that of TOZ.1. The survival of nude mice implanted into the brain with U-87MG tumor cells was markedly prolonged by intratumoral TOIkappaB injection and GCV administration. Survival of TOIkappaB+GCV group was significantly longer (P<.02, Wilcoxon test) than for the control groups (TOZ.1 or TOIkappaB only, PBS or PBS+GCV). These results suggest that IkappaBalphaM expression may be a safe enhancement of replication-defective HSV-based suicide gene therapy in vitro and in vivo.

Chromosomal and genetic abnormalities in benign and malignant meningiomas using DNA microarray.

BACKGROUND: Meningioma is the commonest brain tumor and many genetic abnormalities, such as the loss of chromosome 22q and the mutation of NF2, have been reported. METHODS: These classical abnormalities were detected using Southern blot, PCR, fluorescence in situ hybridization and comparative genomic hybridization, but these methods examine only very limited regions or limited mapping resolution of the tumor genome. In this study, we used DNA microarray assay, which detects numerous genetic abnormalities simultaneously and analyses a global assessment of molecular events in meningioma cells. We studied 31 meningiomas by GenoSensor Array 300 in order to detect the chromosomal aberrations and genetic abnormalities in the whole genome. RESULTS: This study demonstrated not only classical chromosomal aberration, such as loss of chromosome 22q in 19 meningiomas (61.3%), but also new genetic characteristics of meningiomas, such as amplification of MSH2 in 16 meningiomas (51.6%), deletion of GSCL in 13 meningiomas (41.9%) and deletion of HIRA in seven meningiomas (22.6%). CONCLUSIONS: These results suggest that DNA microarray assay is useful in research for the genetic characters of meningiomas and understanding tumorigenesis.

Immunohistochemical detection of female sex hormone receptors in craniopharyngiomas: correlation with clinical and histologic features.

BACKGROUND: Although craniopharyngiomas have a histologically benign nature, their treatment can be difficult. The correlation among clinical, proliferative, and immunohistologic features of female sex hormone receptors was determined in craniopharyngiomas to analyze whether they influence the growth of the tumor. METHODS: The study subjects were 43 patients with previously untreated craniopharyngioma who underwent surgery at our department over the past 15 years. Serial tissue sections were immunostained with the antibodies against estrogen receptor (ER), progesterone receptor (PR), and Ki-67. RESULTS: The Ki-67 labeling index was significantly higher in patients with regrowth (7.8%) than without regrowth (3.9%). ER and PR were detected in 9 of 30 (30%) craniopharyngiomas, and the incidence of postoperative tumor regrowth was significantly higher in patients negative for ER and PR (29%) than in those positive for both receptors (11%). CONCLUSIONS: A high Ki-67 labeling index suggests a high possibility of tumor regrowth, and the presence of ER and PR is suggestive of a high tissue differentiating potential. ER and PR assay may be useful for determining the indication for additional radiation therapy in craniopharyngioma patients treated by incomplete resection.

Frequency-dependent spatial distribution of human somatosensory evoked neuromagnetic fields.

Using synthetic aperture magnetometry (SAM), we examined the spatial distribution of frequency changes in magnetoencephalography signal rhythms on individual magnetic resonance images following somatosensory stimulation. SAM is a novel statistical spatial filtering method that uses an adaptive beamformer. Electrical stimulation of the right median nerve demonstrated high-frequency event-related synchronization (ERS) in the 50-200-Hz range, consistently localized in the contralateral primary sensorimotor area in all subjects (n=7). Event-related desynchronization (ERD) was demonstrated in the 8-13, 13-25 and 25-50-Hz ranges bilaterally in the area surrounding the central sulcus. The differences in the spatial distribution as well as the frequency bands between ERS and ERD suggest that ERS and ERD reflect the responses of different cell assemblies rather than a frequency shift of the same cell assembly.

Volumetric thermal devascularization of large meningiomas.

OBJECT: Controlling hemorrhage is crucial in the safe and efficient removal of large meningiomas. Intravascular embolization is not always a satisfactory means of accomplishing this goal because of the procedure's hemostatic effect and risk of complications. The authors in this study used a volumetric thermal ablation technique incorporating radiofrequency energy, image guidance, and local temperature control to devascularize tumor tissue. METHODS: Five patients with large meningiomas were treated. The target and orientation of the radiofrequency thermal ablation (RFTA) were simulated preoperatively to maximize devascularization of the lesion without thermal injury to adjacent critical structures. Image fusion, three-dimensional reconstruction, and image-guided methods provided for optimized trajectories and targets for insertion of the RFTA needle. During ablation, local temperatures of the tissue being cauterized were monitored continuously to limit the ablated lesion to within the target volume. The effects of devascularization and the softening of the tumor parenchyma facilitated lesion removal. The intracranial ablated meningioma changed into necrotic tissue and shrank within a few months. Histopathological examination of the ablated lesion revealed sharply demarcated coagulation necrosis. CONCLUSIONS: Volumetric thermal devascularization can be applied safely in the treatment of large meningiomas to facilitate surgical manipulation of the lesion as well as to reduce its size palliatively. The procedure's usefulness should be studied further in a larger number of cases with different tumor characteristics.

Brain metastasis from small-cell neuroendocrine carcinoma of the urinary bladder: a case report.

Eight months after radical surgery for small-cell neuroendocrine carcinoma (SCNC) of the urinary bladder, a 69-year-old man was admitted with a brain tumor in the left frontal lobe. The tumor, about 5 cm in diameter, was intensely but heterogeneously enhanced on computed tomography and magnetic resonance imaging. The tumor was subtotally removed, leaving only the portion adjacent to the anterior horn of the left lateral ventricle. Microscopically, the tumor was composed of diffuse sheets of small tumor cells with round to spindle-shaped nuclei, indistinct nucleoli, scant or absent cytoplasm, and indistinct cell margins. Immunohistochemically, the tumor cells were positive for synaptophysin, neuron-specific enolase, chromogranin A, and keratin. Ultrastructurally, the tumor cells showed classic neurosecretory granules and microvilli in the cytoplasm. The tumor was diagnosed as a brain metastasis from SCNC of the urinary bladder. After surgery, whole-brain radiation therapy of 40 Gy was performed, which succeeded in controlling the residual tumor. However, 4 months after surgery, the patient died of meningeal carcinomatosis. To our knowledge, this is the first report focusing on brain metastasis from SCNC of the urinary bladder. The clinicopathological features and pathological diagnosis of this tumor are discussed.

Genetic analysis of human glioblastomas using a genomic microarray system.

Genomic microarray systems can simultaneously provide substantial genetic and chromosomal information in a relatively short time. We have analyzed genomic DNA from frozen sections of 30 cases of primary glioblastomas by GenoSensor Array 300 in order to characterize gene amplifications, gene deletions, and chromosomal information in the whole genome. Genes that were frequently amplified included RFC2/CYLN2 (63.3%), EGFR (53.3%), IL6 (53.3%), ABCB1 (MDR1) (36.7%), and PDGFRA (26.7%). Genes that were frequently deleted included (56.7%), FGFR2 (66.7%), MTAP (60.0%), DMBT1 CDKN2A (p16)/MTAP (50.0%), PIK3CA (43.3%), and EGR2 (43.3%), but deletion of RB1 or TP53 was rarely detected. Chromosomal gains were observed frequently for 7q (33.3%), 7p (20.0%), and 17q (13.3%). Loss of the 10q was frequently detected in 13 of 30 cases (46.7%). Loss of the entire chromosome 10 was seen in 9 of 30 cases (30.0%), and was often accompanied by EGFR amplification (7 cases, 77.8%). The GenoSensor Array 300 proved to be useful for identification of genome-wide molecular changes in glioblastomas. The obtained microarray profile can also yield valuable insight into the molecular events underlying carcinogenesis of brain tumors and may provide clues about clinical correlations, including response to treatment.

Chromosomal and genetic aberrations differ with meningioma subtype.

Meningioma is one of the most common brain tumors, and a variety of genetic abnormalities have been detected by the Southern blotting, polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH) methods. However, these methods detect only a very limited portion of the tumor genome or have a limited mapping resolution. In this study, we used DNA microarray assay, which detects numerous genetic abnormalities and analyzes a global assessment of molecular events in tumor cells. We analyzed genomic DNA from 26 patients with benign meningiomas by GenoSensor Array 300 in order to characterize gene amplifications, gene deletions, and chromosomal information in the whole genome. Loss of chromosome 22q was found most frequently. This chromosomal aberration was detected in 14 meningiomas (53.8%), particularly in transitional and fibrous meningiomas. In meningothelial meningiomas, amplification of INS and TCL1A was detected more frequently than in other meningioma subtypes. DNA microarray assay revealed new genetic differences among the meningioma subtypes, thus indicating that this novel technique is useful for understanding tumor genesis and for the diagnosis of meningioma subtype.