1/7. Oncogene amplification in medulloblastoma: analysis of a case by comparative genomic hybridization and fluorescence in situ hybridization.We describe amplification of the MYCC oncogene in a medulloblastoma with aggressive clinical behavior. The patient was a six year old boy who underwent gross total surgical excision of a cerebellar tumor. Despite chemotherapy and total neuraxis radiation, the clinical course was one of relentless progression, with extensive subarachnoid spread and death within eight months of presentation. The pathological features were consistent with the recently described, "large cell variant" of medulloblastoma. Tumor cells exhibited large vesicular nuclei, prominent nucleoli and strong immunoreactivity for synaptophysin. polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) assay revealed no evidence of MYCN amplification or 1p deletion in the tumor. FISH analysis revealed evidence of MYCC amplification in the 20- to 30-fold range. Comparative genomic hybridization (CGH) revealed regions of gains and amplification in three locations, with gains of chromosome 7, amplification of 8q24 (corresponding to the MYCC locus) and gains of the long arm of chromosome 17 (suggestive of isochromosome 17q). While conventional karyotypic analysis was not successful in the present case, CGH provided invaluable information about gene amplification and losses/gains of chromosomes and chromosomal regions. Thus, CGH is a powerful technique applicable to frozen or paraffin-embedded material which helps to ascertain the presence of gene amplification even without prior knowledge of the gene to be tested.- - - - - - - - - - ranking = 1keywords = amplification (Clic here for more details about this article) |
2/7. Multiple genomic alterations including N-myc amplification in a primary large cell medulloblastoma.The large cell (LC) subtype is a recently described histologic variant of medulloblastoma (Mb) associated with a rapid and aggressive clinical course. We describe the genomic profile of a LC-Mb tumor obtained from a patient who developed recurrent and fulminant disease despite 'good-risk' features at diagnosis and state- of-the-art multidisciplinary therapy. The tumor sample was analyzed using comparative genomic hybridization (CGH) and complementary molecular approaches. CGH revealed amplicons at chromosome bands 2p24-25, 2q12-22, and 17p11; losses of chromosomes 11q and 18; and low-level gains of 3q, 11p, 13q and 14q. Southern blot analysis confirmed N-myc amplification. No evidence of p53 mutation was detected. The genomic profile of this LC-Mb tumor sample revealed a distinctive pattern of genetic alterations including amplification of N-myc and anonymous oncogenes at chromosome bands 2q12-22 and 17p11. These genomic abnormalities are uncommon in other subtypes of Mb.- - - - - - - - - - ranking = 0.54545454545455keywords = amplification (Clic here for more details about this article) |
3/7. comparative genomic hybridization of medulloblastomas and clinical relevance: eleven new cases and a review of the literature.Medulloblastomas are highly malignant primitive neuroectodermal tumors of the cerebellum that display a wide variety of histopathological patterns. However, these patterns do not provide an accurate prediction of clinical-biological behavior and no satisfactory morphological grading system has ever been presented. Genetic alterations may provide additional diagnostic information and allow clinically relevant subgrouping of primitive neuroectodermal tumors. We examined 10 medulloblastomas and one medulloblastoma cell line. One amplification site on chromosome 8q24 was detected in the cell line corresponding to the known amplification of the c-myc gene in this cell line. The gain of 2p21-24 in two tumors was shown to represent amplification of the N-myc gene by Southern blot hybridization and fluorescence in situ hybridization. The data show that the isochromosome 17 can be recognized using comparative genomic hybridization (CGH) by the typical combination of loss of 17p combined with gain of 17q. No specific pattern of genetic alterations could be linked to the clinical behavior of the tumors. We have compared our results with previous CGH studies on medulloblastomas.- - - - - - - - - - ranking = 0.27272727272727keywords = amplification (Clic here for more details about this article) |
4/7. Large cell/anaplastic medulloblastomas and medullomyoblastomas: clinicopathological and genetic features.OBJECT: medulloblastoma is the most common malignant central nervous system neoplasm found in children. A distinct variant designated large cell/anaplastic (LC/A) medulloblastoma is characterized by frequent dissemination of cerebrospinal fluid (CSF) at presentation and a more aggressive clinical course. The authors report on their examination of the clinicopathological and genetic features of seven such cases encountered at their institution. methods: Eighty cases of medulloblastomas were reviewed and seven (8.8%) of these were believed to fit the histological and immunohistochemical criteria for LC/A medulloblastoma. In three cases (43%) either desmoplastic or classic medulloblastoma was the underlying subtype, and in two cases (28%) the LC/A tumor was found within the setting of medullomyoblastoma. fluorescence in situ hybridization was used in six of the seven cases to characterize the presence of isochromosome 17q, deletion of chromosome 22q (a deletion characteristically found in atypical teratoid/rhabdoid tumors), and c-myc amplification. The patients' clinical histories revealed CSF dissemination in all cases and lymph node metastasis in one case. Isochromosome 17q was found in five (83%) of six cases. Evidence of chromosomal gains indicated aneuploidy in three tumors (50%), and amplification of c-myc was found in three tumors (50%). No 22q deletions were encountered. CONCLUSIONS: A high percentage of LC/A medulloblastomas arise within a background of typical medulloblastomas or medullomyoblastomas. As is the case in conventional medulloblastomas, the presence of 17q is a common early tumorigenic event; however, in a significant percentage of specimens there is also evidence of aneuploidy and/or amplification of c-myc. These findings indicate that LC/A morphological characteristics reflect a more advanced tumor stage than that found in pure medulloblastomas or in typical medullomyoblastomas.- - - - - - - - - - ranking = 0.27272727272727keywords = amplification (Clic here for more details about this article) |
5/7. radiation-induced cerebellar glioblastoma at the site of a treated medulloblastoma: case report.radiation-induced glioblastoma multiforme (GBM) is a rare complication of radiotherapy. The authors report such a case occurring 10 years after treatment of cerebellar medulloblastoma. The patient was a 15-year-old boy who had undergone a gross-total removal of a medulloblastoma and received radiation therapy at the age of 5 years. He had experienced no tumor recurrences for 10 years until a new enhancing mass was found at the original site of the medulloblastoma. Following its resection the new lesion was found to be a GBM and there was no evidence of a medulloblastoma. The second tumor developed at the same site as the previous one after a sufficient latent period and fulfilled the criteria for a radiation-induced neoplasm. The original tumor cells expressed synaptophysin without p53 overexpression, a characteristic feature of medulloblastomas. In contrast, cells from the later tumor expressed glial fibrillary acidic protein and p53 but not synaptophysin. A sequence analysis of the p53 gene showed deletion at codon 233 and a C to G transition at codon 278 in the GBM but no mutation in the medulloblastoma. A GBM specimen revealed no amplification of the epidermal growth factor receptor compared with a normal control specimen. In conclusion, the clinical features of a radiation-induced GBM are similar to that of the primary GBM, whereas its genetic alterations render it a secondary GBM. These findings indicate that radiation-induced GBM should be considered a distinct clinical entity.- - - - - - - - - - ranking = 0.090909090909091keywords = amplification (Clic here for more details about this article) |
6/7. Molecular cytogenetic analysis of a medulloblastoma with isochromosome 17 and double minutes.cytogenetic analysis of a medulloblastoma revealed two abnormal cell lines of 48,XY, 8, 8, -14, der(14)t(1;14)(q11;p11),i(17q) and 51,XY, 5, 6, 8, 8, -14 20, der (14)t(1;14)(q11;p11),i(17q), dmin. The finding of double minute chromosomes in some medulloblastomas has been associated with amplification of the c-myc or N-myc oncogenes. We were unable to detect gene amplification with these probes by Southern blot analysis.- - - - - - - - - - ranking = 0.18181818181818keywords = amplification (Clic here for more details about this article) |
7/7. Aggressive medulloblastoma with high-level N-myc amplification.A 27-year-old man was treated for an aggressive cerebellar medulloblastoma that, at operation, exhibited dural invasion. Six months after gross total resection and radiation therapy, a "surgical metastasis" developed in the lower portion of the surgical scar. The tumor grew rapidly down into the right side of his neck. Chemotherapy failed, and he subsequently died. Cytogenetic and molecular genetic studies revealed multiple numeric and structural chromosome abnormalities, including an abnormal chromosome 17p arm, more than 100-fold N-myc amplification, a rearranged c-myc gene, and a 16-base pair deletion involving exon 7 of the p53 gene. We postulate that these genetic features may have contributed to the aggressive behavior of the tumor.- - - - - - - - - - ranking = 0.45454545454545keywords = amplification (Clic here for more details about this article) |