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IntroductionHodgkin lymphoma (HL), which accounts for approximately one third of all malignant lymphomas, is characterized by the presence of only a small fraction of malignant cells. Neoplastic cells represented as mononucleated Hodgkin-and multinucleated Reed-Sternberg cells (HRS cells) are embedded in a varying infiltrate of reactive cells including B and T lymphocytes, eosinophils, plasma cells, and fibroblasts. 1 According to the new World Health Organization (WHO) classification, 2 4 well-defined histotypes of classical Hodgkin lymphoma (cHL) can be distinguished: lymphocyte-rich (cHL-LR), nodularsclerosis (cHL-NS), mixed-cellularity (cHL-MC), and lymphocytedepletion (cHL-LD). Paragranuloma (nodular lymphocyte predominant Hodgkin lymphoma [NLPHL]) has been shown to be clinically and immunophenotypically distinct and eventually to transform to large B-cell non-Hodgkin lymphoma. This indicates that NLPHL is essentially different from the cHL subtypes.Because of the small number of malignant cells, cytogenetic analysis is particularly difficult in HL and, to date, has not revealed any specific chromosomal rearrangements. Detailed analysis by chromosome banding is further limited by the low mitotic index of neoplastic cells, frequently poor chromosome morphology, and complex karyotypic rearrangements. For these reasons, it is difficult to obtain sufficient numbers of karyotypes for evaluation that are representative of the malignant cell population. 3,4 Alternatively, combined immunohistochemical and cytogenetic analyses by fluorescence in situ hybridization (FISH) have been applied. It could be demonstrated that chromosomal changes are almost exclusively restricted to CD30 ϩ HRS cells. Furthermore, significant heterogeneity in terms of the copy number of single chromosomes was detected using this approach. [5][6][7][8] Recently, comparative genomic hybridization (CGH) was applied in combination with universal polymerase chain reaction (PCR) technology for cytogenetic analyses of HRS cells. 9-11 These analyses indicated higher rates of numerical aberrations of individual chromosomes than had previously been found by banding analysis, in which the identification of numerical changes is difficult because of the complex karyotypes of HRS cells. Gains and losses in more than 50% of the cHL tumors were identified on chromosomal arms 2p, 7q, and 16q, 9,10 whereas in NLPHL, chromosomal arms 1q, 3p, 5q, and Xq were affected. 11 Although the number of analyses is still low (20 cHLs and 20 NLPHLs to date), CGH has already allowed the identification of several imbalanced chromosomal subregions, indicating the localization of candidate genes that may be involved in the etiology of this disease.To further define critical subregions in cHL, a series of 41 tumors was analyzed (a small subset of cases was reported recently 10 ). To this end, collected pools of approximately 30 malignant HRS cells from single tumors were isolated using microdissection technology. Genomic DNA from the individual cell pools was subsequently ampl...

To elucidate the molecular events responsible for tumorigenesis and progression of ependymomas, we analyzed molecular alterations on the gene expression level in a series of newly diagnosed ependymal neoplasms (n ‫؍‬ 39). To this aim, tumor RNA was hybridized to microarrays comprising 2600 different genes with relevance to mitosis, cell-cycle control, oncogenesis, or apoptosis. For CLU, IGF-2, and RAF-1, which are apparent candidate genes because they had been previously described to be involved in tumorigenesis of other human malignancies, we found a high expression on the mRNA as well as the protein level. We identified gene expression signatures for the differentiation of tumors with respect to location, grade, and patient age. Spinal ependymomas were characterized by high-expression levels of HOXB5, PLA2G, and CDKN2A and tumors in young patients (<16 years of age) by high-expression levels of LDHB and STAM. Notably, we were able to classify supratentorial grade II and III tumors with 100% accuracy, whereas this did not apply for infratentorial Ependymal tumors arise from the ependymal lining of the cerebral ventricles and from the remnants of the central canal of the spinal cord. This neoplasm constitutes ϳ3 to 5% of all intracranial malignancies and is the third most common brain tumor in children and young adults. 1,2 In ependymomas, the morphological features and biological behavior vary considerably. Patients with spinal tumor location have usually a favorable prognosis after gross total resection, whereas local tumor progression is the predominant reason for death in patients with intracranial ependymomas, resulting in a 5-year overall survival of ϳ60%. [3][4][5] Because ependymomas are characterized by tremendous variability in clinical behavior, the understanding of the complex changes taking place at the genomic level might lead to more precise understanding of the tumor biology. Cytogenetic studies revealed numerous chromosomal aberrations in ependymomas. In particular, a 30 to 50% incidence of aberrations involving chromosome 22, including monosomy 22 as well as deletions of 22q, prevailed the most frequent finding. 6 -8 Recently, Hirose and co-workers 7 reported on different patterns of chromosomal abnormalities with respect to tumor location detected by comparative genomic hybridization. In intracranial tumors, gain of 1q and losses on 6q, 9, and 13 were frequent, whereas gains on chromosome 7 were recognized almost exclusively in spinal cord tumors and were associated with various other chromosomal aberrations including frequent loss of 22q, suggesting that intracranial and spinal cord ependymomas progress along substantially different pathways. As a hereditary form, neurofibromatosis type 2 is associated with spinal ependymomas, indicating a functional role of the NF2 tumor suppressor gene in these tumors. 9,10 In contrast to adults in which spinal tumors predominate, ϳ90% of all pediatric ependymomas are of intraSupported by the Bundesministerium fü r Bildung und Forschung (FKZ 01 KW 9937 and...