Insights revealed by high-throughput genomic arrays in nonglial primary brain tumors.
ABSTRACT Primary CNS tumors (PCNSTs) encompass a broad and heterogeneous group of tumors, including gliomas, meningiomas, embryonal tumors, primary CNS lymphomas, CNS germ cell tumors and sellar region tumors. In recent decades, research has focused on understanding the clinical and biological significance of molecular abnormalities detected in PCNSTs. The emergence of genomic arrays, including comparative genomic hybridization and SNP arrays, have helped in the discovery of novel critically important genes and novel genomic biomarkers involved in PCNST oncogenesis (e.g., BRAF duplication in pilocytic astrocytoma). Since a summary of data from genomic arrays using gliomas has been described in a previous review, in this article we will focus on the insights provided by genome-wide DNA arrays in the genetics and genomics of nonglial PCNSTs in adults. The high-throughput assessment of gene copy-number abnormalities has improved our knowledge of molecular pathogenesis in nonglial PCNSTs, allowing for the identification of new candidate genomic regions and genes involved in tumorigenesis. These chromosome imbalances provide a promising insight into potential targets for innovative drugs and new interesting diagnostic and prognostic biomarkers for clinical practice.
Article: Central neurocytoma: a review.[Show abstract] [Hide abstract]
ABSTRACT: Central neurocytomas are rare intraventricular neoplasms of the central nervous system, compromising 0.25-0.5% of brain tumors. The diagnosis and management of these tumors remains controversial since most clinical series are small. Typically, patients with central neurocytomas have a favorable prognosis, but in some cases the clinical course is more aggressive. Although histological features of anaplasia do not predict biologic behavior, proliferation markers including MIB-1 might be more useful in predicting relapse. The most important therapeutic modality is surgery, and a safe maximal resection confers the best long-term outcome. In cases of a subtotal resection,'standard external beam radiation can be added or radiation can be delayed until tumor progression occurs. Smaller residual tumor volumes or recurrences can be treated with more conformal radiation or focused radiosurgery. Re-operation for recurrence should be considered if the procedure can be safely performed. Chemotherapy may be useful for recurrent central neurocytomas that cannot be resected and have been radiated, although long-term responses have not been reported for chemotherapy. Overall, this paper reviews the findings of the larger studies and highlights some of the important case reports that contribute to the current management of central neurocytomas.Journal of Neuro-Oncology 03/2004; 66(3):377-84. DOI:10.1023/B:NEON.0000014541.87329.3b · 2.79 Impact Factor
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ABSTRACT: Despite intensive therapy, the survival of children with medulloblastoma remains disappointing. Moreover, children who survive are affected by serious long-term sequelae of treatment that impair their quality of life. In search of chromosomal aberrations indicative of sites involved in oncogenic transformation and in an attempt to find reliable prognostic markers, the authors analyzed 15 medulloblastomas by comparative genomic hybridization. All neoplasms showed chromosomal abnormalities. The most frequent losses were 17p (7/15 tumors), 8p and 11p (6/15), 10p, 1lq, 16q, and 20q (5/15), and 20p (4/15). Gains were recurrently found at 7q (10/15 tumors), 17q and 18q (9/15 tumors), 7p and 13q (7/15), 18p (6/15), and 1q, 4q, 6q. and 9p (5/15 tumors). Four tumors showed loss of 17p together with gain of 17q, suggesting an isochromosome 17q. High-level amplifications were seen at 1p34, 5p15, 13q34, and 18p11 (one tumor each), and at 2p15 in two tumors, one of which was proven to be N-Myc amplification. The overall pattern of alterations found in this study confirms the findings of other studies and adds two novel regions with chromosomal gains, at 13q and 18q. Previous reports on the relation between 17q gain and survival could not be confirmed, whereas amplification of N-myc or L-myc seems to indicate poor clinical outcome.Journal of Pediatric Hematology/Oncology 01/2002; 24(3):205-10. DOI:10.1097/00043426-200203000-00009 · 0.96 Impact Factor
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ABSTRACT: Fifty-one primary intracranial germ cell tumors (GCT), including germinoma, teratoma, endodermal sinus tumor, choriocarcinoma and mixed GCT, were studied. The incidence of GCT in the surgically removed intracranial neoplasms was 11.1% for pediatric patients and 0.6% for adult patients. The age/sex of the patients and the location of the tumors were analyzed. Morphologic findings of these tumors were identical to that of their gonadal counterparts. Immunohistochemical studies showed that alpha-fetoprotein (alpha-AFP), human chorionic gonadotropin (HCG), and placental alkaline phosphatase (PLAP) were helpful, whereas carcinoembryonic antigen (CEA) and cytokeratin (CKER) were of little help in determining the diagnosis. Serum tumor markers, alpha-AFP and HCG, were helpful in recognizing GCT producing them. However, they could not be used for specific diagnosis because different tumors could have similar serum levels. Histopathologic study was handicapped by the small size of most specimens (which usually could not include all of the components if the tumor was a mixed GCT), but it was the only means for specific diagnosis.Cancer 10/1992; 70(6):1577-84. DOI:10.1002/1097-0142(19920915)70:63.0.CO;2-X · 4.90 Impact Factor