Molecular analyses of glioblastoma stem-like cells and glioblastoma tissue.

Glioblastoma is a common, malignant brain tumor whose disease incidence increases with age. Glioblastoma stem-like cells (GSCs) are thought to contribute to cancer therapy resistance and to be responsible for tumor initiation, maintenance, and recurrence. This study utilizes both SNP array and gene expression profiling to better understand GSCs and their relation to malignant disease. Peripheral blood and primary glioblastoma tumor tissue were obtained from patients, the latter of which was used to generate GSCs as well as a CD133pos./CD15pos. subpopulation. The stem cell features of GSCs were confirmed via the immunofluorescent expression of Nestin, SOX2, and CD133. Both tumor tissue and the isolated primary cells shared unique abnormal genomic characteristics, including a gain of chromosome 7 as well as either a partial or complete loss of chromosome 10. Individual genomic differences were also observed, including the loss of chromosome 4 and segmental uniparental disomy of 9p24.3→p21.3 in GSCs. Gene expression profiling revealed 418 genes upregulated in tumor tissue vs. CD133pos./CD15pos. cells and 44 genes upregulated in CD133pos./CD15pos. cells vs. tumor tissue. Pathway analyses demonstrated that upregulated genes in CD133pos./CD15pos. cells are relevant to cell cycle processes and cancerogenesis. In summary, we detected previously undescribed genomic and gene expression differences when comparing tumor tissue and isolated stem-like subpopulations.

Central neurocytoma: SNP array analyses, subtel FISH, and review of the literature.

The central neurocytoma (CN) is a rare brain tumor with a frequency of 0.1-0.5% of all brain tumors. According to the World Health Organization classification, it is a benign grade II tumor with good prognosis. However, some CN occur as histologically "atypical" variant, combined with increasing proliferation and poor clinical outcome. Detailed genetic knowledge could be helpful to characterize a potential atypical behavior in CN. Only few publications on genetics of CN exist in the literature. Therefore, we performed cytogenetic analysis of an intraventricular neurocytoma WHO grade II in a 39-year-old male patient by use of genome-wide high-density single nucleotide polymorphism array (SNP array) and subtelomere FISH. Applying these techniques, we could detect known chromosomal aberrations and identified six not previously described chromosomal aberrations, gains of 1p36.33-p36.31, 2q37.1-q37.3, 6q27, 12p13.33-p13.31, 20q13.31-q13.33, and loss of 19p13.3-p12. Our case report contributes to the genetic knowledge about CN and to increased understanding of "typical" and "atypical" variants.

Interaction of quality of life, mood and depression of patients and their informal caregivers after surgical treatment of high-grade glioma: a prospective study.

INTRODUCTION: Patients who are diagnosed with high-grade gliomas (HGG) have poor prognoses and often experience rapid declines in functional and cognitive status, which makes caring for them particularly stressful. We conducted a prospective study to investigate the factors influencing the quality of life of HGG patients and their informal caregivers and analyzed their reciprocal impacts. Based on our results, we elaborated a screening model to identify patients and caregivers in need of psychooncological support. METHODS: A total of 45 matched HGG patient-caregiver dyads completed the Multidimensional Mood State Questionnaire, the 12-Item Short Form Medical Outcome Questionnaire and the Center for Epidemiology Studies Depression Scale. A subsequent semi-structured interview was performed with each individual. RESULTS: We found a significant relationship between the mood and depression scores of patients and caregivers, with a third of them displaying symptoms of a major depressive episode. Our screening model showed that 73% of the dyads exhibited signs of severe emotional strain with the need of psychooncological support. Beneficial factors that helped patients and caregivers cope with the illness included mutual respect, good communication, caregiver mastery and resilience. CONCLUSIONS: For a more comprehensive understanding of patient-caregiver interactions, we recommend using a combination of standardized psychometric tests and a semi-structured interview. The high percentage of emotional strain and depression found in patients and their caregivers facing HGG highlights the necessity of methodical screening for warning signs and consequent initiation of psycho-oncological interventions.

Three gangliogliomas: results of GTG-banding, SKY, genome-wide high resolution SNP-array, gene expression and review of the literature.

According to the World Health Organization gangliogliomas are classified as well-differentiated and slowly growing neuroepithelial tumors, composed of neoplastic mature ganglion and glial cells. It is the most frequent tumor entity observed in patients with long-term epilepsy. Comprehensive cytogenetic and molecular cytogenetic data including high-resolution genomic profiling (single nucleotide polymorphism (SNP)-array) of gangliogliomas are scarce but necessary for a better oncological understanding of this tumor entity. For a detailed characterization at the single cell and cell population levels, we analyzed genomic alterations of three gangliogliomas using trypsin-Giemsa banding (GTG-banding) and by spectral karyotyping (SKY) in combination with SNP-array and gene expression array experiments. By GTG and SKY, we could confirm frequently detected chromosomal aberrations (losses within chromosomes 10, 13 and 22; gains within chromosomes 5, 7, 8 and 12), and identify so far unknown genetic aberrations like the unbalanced non-reciprocal translocation t(1;18)(q21;q21). Interestingly, we report on the second so far detected ganglioglioma with ring chromosome 1. Analyses of SNP-array data from two of the tumors and respective germline DNA (peripheral blood) identified few small gains and losses and a number of copy-neutral regions with loss of heterozygosity (LOH) in germline and in tumor tissue. In comparison to germline DNA, tumor tissues did not show substantial regions with significant loss or gain or with newly developed LOH. Gene expression analyses of tumor-specific genes revealed similarities in the profile of the analyzed samples regarding different relevant pathways. Taken together, we describe overlapping but also distinct and novel genetic aberrations of three gangliogliomas.

Two cases of atypical meningioma with pulmonary metastases: a comparative cytogenetic analysis of chromosomes 1p and 22 and a review of the literature.

We present two cases of atypical meningioma WHO grade II with a history of multiple local recurrences and late pulmonary metastases. Comparative cytogenetic analyses on 1p and 22q confirmed clonal origin of the primary intracranial meningiomas and the pulmonary metastases in both cases. These cases illustrate the importance of close neuroradiological follow-up to detect tumor recurrence in patients with atypical meningiomas WHO grade II even with clinically stable disease and should sensitize clinicians to late extracranial metastases of these tumors, especially to the lung. In an effort to elucidate common clinical features of metastatic meningiomas, especially to the lung, the literature was reviewed from 1995 to 2014, identifying a total of 45 published cases.

WHO grade related expression of TRAIL-receptors and apoptosis regulators in meningioma.

BACKGROUND AND AIMS: The expression of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors and key regulators of the extrinsic apoptosis pathway correlate with clinical features and the WHO grade of malignancy in some tumor entities. Expression of pro-apoptotic TRAIL receptors and executioners of apoptosis are a prerequisite for TRAIL-based therapies as a promising future targeted therapy. METHODS: Human meningioma tissues (n=24 WHO grade I, n=7 WHO grade II, n=6 WHO grade III) were immunohistochemically analyzed for the expression of TRAIL-R1, TRAIL-R2, TRAIL-R3, TRAIL-R4, caspase-8, cFLIP, Bcl-2, Bcl-XL, Mcl-1, Bax, and Bak. Staining intensities were quantified by an automated software-based algorithm. RESULTS: While TRAIL-R1 and TRAIL-R3 were nearly absent in meningiomas, TRAIL-R2 and TRAIL-R4 were abundantly expressed. However, only TRAIL-R4 expression correlated with the WHO grade of malignancy. Bcl-2 showed a non-significant upregulation in WHO grade III meningiomas. Bcl-XL and Mcl-1 expression was significantly higher in WHO grade II compared to grade I. Bcl-XL and TRAIL-R4 expression correlated with the mitotic activity (Ki67) of the tumor. Furthermore, TRAIL-R2 expression correlated with TRAIL-R4. Bak expression correlated with both, Bcl-XL and Mcl-1 expression. The expression patterns did neither correlate with the progression-free nor with the overall survival of the meningioma patients. CONCLUSIONS: Apoptosis-inducing TRAIL-R2 and all key executioners of the extrinsic apoptosis pathway are abundantly expressed in meningioma. For some regulators of apoptosis with opposite functions, the expression of the pro-apoptotic protein significantly correlated with the expression level of the respective anti-apoptotic binding partner, possibly resulting in a steady-state of apoptosis. TRAIL-R2 might serve as a novel therapeutic target in meningioma.

Bortezomib sensitizes primary meningioma cells to TRAIL-induced apoptosis by enhancing formation of the death-inducing signaling complex.

A meningioma is the most common primary intracranial tumor in adults. Here, we investigated the therapeutic potential of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in 37 meningiomas. Freshly isolated primary meningioma cells were treated with TRAIL with or without different sensitizing protocols, and apoptotic cell death was then quantified. Mechanisms of TRAIL sensitization were determined by a combination of Western blotting, flow cytometry, receptor complex immunoprecipitation, and siRNA-mediated knockdown experiments. Tumor necrosis factor-related apoptosis-inducing ligand receptor expression was analyzed using immunohistochemistry and quantified by an automated software-based algorithm. Primary tumor cells from 11 (29.7%) tumor samples were sensitive to TRAIL-induced apoptosis, 12 (32.4%) were intermediate TRAIL resistant, and 14 (37.8%) were completely TRAIL resistant. We tested synergistic apoptosis-inducing cotreatment strategies and determined that only the proteasome inhibitor bortezomib potently enhanced expression of the TRAIL receptors TRAIL-R1 and/or TRAIL-R2, the formation of the TRAIL death-inducing signaling complex, and activation of caspases; this treatment resulted in sensitization of all TRAIL-resistant meningioma samples to TRAIL-induced apoptosis. Bortezomib pretreatment induced NOXA expression and downregulated c-FLIP, neither of which caused the TRAIL-sensitizing effect. Native TRAIL receptor expression could not predict primary TRAIL sensitivity. This first report on TRAIL sensitivity of primary meningioma cells demonstrates that TRAIL/bortezomib cotreatment may represent a novel therapeutic option for meningiomas.

Cell cycle, oncogenic and tumor suppressor pathways regulate numerous long and macro non-protein-coding RNAs.

BACKGROUND: The genome is pervasively transcribed but most transcripts do not code for proteins, constituting non-protein-coding RNAs. Despite increasing numbers of functional reports of individual long non-coding RNAs (lncRNAs), assessing the extent of functionality among the non-coding transcriptional output of mammalian cells remains intricate. In the protein-coding world, transcripts differentially expressed in the context of processes essential for the survival of multicellular organisms have been instrumental in the discovery of functionally relevant proteins and their deregulation is frequently associated with diseases. We therefore systematically identified lncRNAs expressed differentially in response to oncologically relevant processes and cell-cycle, p53 and STAT3 pathways, using tiling arrays. RESULTS: We found that up to 80% of the pathway-triggered transcriptional responses are non-coding. Among these we identified very large macroRNAs with pathway-specific expression patterns and demonstrated that these are likely continuous transcripts. MacroRNAs contain elements conserved in mammals and sauropsids, which in part exhibit conserved RNA secondary structure. Comparing evolutionary rates of a macroRNA to adjacent protein-coding genes suggests a local action of the transcript. Finally, in different grades of astrocytoma, a tumor disease unrelated to the initially used cell lines, macroRNAs are differentially expressed. CONCLUSIONS: It has been shown previously that the majority of expressed non-ribosomal transcripts are non-coding. We now conclude that differential expression triggered by signaling pathways gives rise to a similar abundance of non-coding content. It is thus unlikely that the prevalence of non-coding transcripts in the cell is a trivial consequence of leaky or random transcription events.

Comprehensive high-resolution genomic profiling and cytogenetics of two pediatric and one adult medulloblastoma.

Medulloblastoma (WHO grade IV) is a rare, malignant, invasive, embryonal tumor which mainly occurs in children and represents less than 1% of all adult brain tumors. Systematic comprehensive genetic analyses on medulloblastomas are rare but necessary to provide more detailed information. Therefore, we performed comprehensive cytogenetic analyses (blood and tissue) of two pediatric and one adult medulloblastoma, using trypsin-Giemsa staining, spectral karyotyping (tissues only), SNP-arrays, and gene expression analyses. We confirmed frequently detected chromosomal aberrations in medulloblastoma, such as +7q, -8p/q, -9q, -11q, -12q, and +17q and identified novel genetic events. Applying SNP-array, we identified constitutional de novo losses 5q21.1, 15q11.2, 17q21.31, 19p12 (pediatric medulloblastoma), 9p21.1, 19p12, 19q13.3, 21q11.2 (adult medulloblastoma) and gains 16p11.1-16p11.2, 18p11.32, Yq11.223-Yq11.23 (pediatric medulloblastoma), Xp22.31 (adult medulloblastoma) possibly representing inherited causal events for medulloblastoma formation. We show evidence for somatic segmental uniparental disomy in regions 1p36, 6q16.3, 6q24.1, 14q21.2, 17p13.3, and 17q22 not previously described for primary medulloblastoma. Gene expression analysis supported classification of the adult medulloblastoma to the WNT-subgroup and classification of pediatric medulloblastomas to group 3 tumors. Analyses of tumors and matched normal tissues (blood) with a combination of complementary techniques will help to further elucidate potentially causal genetic events for medulloblastomas.

Detection of novel genomic aberrations in anaplastic astrocytomas by GTG-banding, SKY, locus-specific FISH, and high density SNP-array.

Astrocytomas represent the largest and most common subgroup of brain tumors. Anaplastic astrocytoma (WHO grade III) may arise from low-grade diffuse astrocytoma (WHO grade II) or as primary tumors without any precursor lesion. Comprehensive analyses of anaplastic astrocytomas combining both cytogenetic and molecular cytogenetic techniques are rare. Therefore, we analyzed genomic alterations of five anaplastic astrocytomas using high-density single nucleotide polymorphism arrays combined with GTG-banding and FISH-techniques. By cytogenetics, we found 169 structural chromosomal aberrations most frequently involving chromosomes 1, 2, 3, 4, 10, and 12, including two not previously described alterations, a nonreciprocal translocation t(3;11)(p12;q13), and one interstitial chromosomal deletion del(2)(q21q31). Additionally, we detected previously not documented loss of heterozygosity (LOH) without copy number changes in 4/5 anaplastic astrocytomas on chromosome regions 5q11.2, 5q22.1, 6q21, 7q21.11, 7q31.33, 8q11.22, 14q21.1, 17q21.31, and 17q22, suggesting segmental uniparental disomy (UPD), applying high-density single nucleotide polymorphism arrays. UPDs are currently considered to play an important role in the initiation and progression of different malignancies. The significance of previously not described genetic alterations in anaplastic astrocytomas presented here needs to be confirmed in a larger series.

Giant intradiploic epidermoid cyst with large osteolytic lesions of the skull: a case report.

INTRODUCTION: We report a case of tumor growth over a period of four decades, presenting with large multicentric lytic lesions of the skull and a profound mass effect, without neurological deficits. Clinical and radiological features of a patient with a giant intradiploic epidermoid and its impact on the choice of treatments are discussed. CASE PRESENTATION: An 81-year-old Caucasian man, who had first noticed a painless subcutaneous swelling over the left frontal scalp about 40 years ago, presented after a short episode of dizziness, which he experienced after treatment of focal retinal detachment. Computed tomography (CT) and magnetic resonance imaging (MRI) examinations revealed an exceptionally large tumor involving major parts of the skull with extensive destruction of the bone and distinct deformation of the brain. Considering his age and the absence of neurological deficits or pain, the patient refused the option of tumor removal and cranioplasty, yet agreed to a biopsy, which confirmed the suspected diagnosis. CONCLUSIONS: The course of the disease demonstrates that even patients with large tumors, inducing distinct pathomorphological changes, do not necessarily experience significant impairment of their quality of life without surgery. This is an impressive example of the chance to lead a long and satisfying life without specific medical treatment, avoiding the inherent risks of these procedures. Yet, there is a clear indication for surgery of intradiploic epidermoids in most cases described in the literature.

High resolution genomic profiling and classical cytogenetics in a group of benign and atypical meningiomas.

Meningiomas are classified as benign, atypical, or anaplastic. The majority are sporadic, solitary, and benign tumors with favorable prognoses. However, the prognosis for patients with anaplastic meningiomas remains less favorable. High resolution genomic profiling has the capacity to provide more detailed information. Therefore, we analyzed genomic aberrations of benign and atypical meningiomas using single nucleotide polymorphism (SNP) array, combined with G-banding by trypsin using Giemsa stain (GTG banding), spectral karyotyping, and locus-specific fluorescence in situ hybridization (FISH). We confirmed frequently detected chromosomal aberrations in meningiomas and identified novel genetic events. Applying SNP array, we identified constitutional de novo loss or gain within chromosome 22 in three patients, possibly representing inherited causal events for meningioma formation. We show evidence for somatic segmental uniparental disomy in regions 4p16.1, 7q31.2, 8p23.2, and 9p22.1 not previously described for primary meningioma. GTG-banding and spectral karyotyping detected a novel balanced reciprocal translocation t(4;10)(q12;q26) in one benign meningioma. A paracentric inversion within 1p36, previously described as novel, was detected as a recurrent chromosomal aberration in benign and atypical meningiomas. Analyses of tumors and matched normal tissues with a combination of SNP arrays and complementary techniques will help to further elucidate potentially causal genetic events for tumorigenesis of meningioma.

Intracranial hemangiopericytoma: Case study with cytogenetics and genome wide SNP-A analysis.

The tumor entity of hemangiopericytoma is not universally recognized as a nosological entity by pathologists, and there is a trend toward reassigning it to other categories gradually. However, hemangiopericytomas occurring in the nervous system are included in the new WHO classification of brain tumors, and are distinguished from both meningioma and fibrous tumors. Since there are few genetic studies, we performed a comprehensive cytogenetic analysis of an infratentorial hemangiopericytoma in a 55-year-old female. It was originally classified as a grade II tumor but recurred as a grade III tumor with a proliferation index of 20%. Using trypsin-Giemsa staining (GTG-banding) and multicolor fluorescence in situ hybridization (M-FISH), we could confirm the loss of chromosomal material 10q, which has been previously described in hemangiopericytoma, and we identified de novo chromosomal aberrations on chromosome 8. Applying genome-wide high-density single nucleotide polymorphism array (SNP-A) analysis, we detected segments with loss or gain, as well as clonal deletions or regions suggestive of segmental uniparental disomy. These findings, together with the results of conventional histological and immunohistochemical characterization, provide additional evidence for the nosological separation of hemangiopericytoma in the central nervous system as a biologically different entity.

Multiple meningioma with different grades of malignancy: case report with genetic analysis applying single-nucleotide polymorphism array and classical cytogenetics.

Multiple meningiomas with synchronous tumor lesions represent only 1-9% of all meningiomas and usually show a uniform histology. The simultaneous occurrence of different grades of malignancy in these nodules is observed in only one third of multiple meningiomas. We report a case of a sporadic multiple meningioma presenting with different histopathological grades (WHO I and II). The tumor genome of both nodules was analyzed by GTG-banding, spectral karyotyping (SKY), locus-specific FISH, and single nucleotide polymorphism array (SNP-A) karyotyping. GTG-banding and SKY revealed 25 structural and 33 numerical aberrations with a slightly increased aberration frequency in the WHO grade II nodule. We could confirm terminal deletions on chromosomes 1p [ish del(1)(p36)(p58-,pter-) 16.5% WHO grade I and 20.9% WHO grade II], partial deletions on 22q, and/or monosomy 22 (monosomy 22 14% WHO grade I and 34% WHO grade II) as the most frequent aberrations in both meningioma nodules. In the meningioma WHO grade II, in addition, a de novo paracentric inversion within chromosomal band 1p36 was detectable. Furthermore, for meningiomas de novo, dicentric chromosomes 4 could be identified in both tumor nodules. We also detected previously published segmental uniparental disomy regions 1p31.1, 6q14.1, 10q21.1, and 14q23.3 in normal control DNA of the patient and in both tumor nodules. Taken together, we describe a very rare case of multiple meningioma with overlapping but also distinct genetic aberration patterns in two nodules of different WHO grades of malignancy.

Bortezomib sensitizes primary human esthesioneuroblastoma cells to TRAIL-induced apoptosis.

TNF-related apoptosis-inducing ligand (TRAIL), a promising novel anti-cancer cytokine of the TNF superfamily, and Bortezomib, the first-in-class clinically used proteasome inhibitor, alone or in combination have been shown to efficiently kill numerous tumor cell lines. However, data concerning primary human tumor cells are very rare. Using primary esthesioneuroblastoma cells we analyzed the anti-tumor potential and the mechanism employed by Bortezomib in combination with TRAIL for the treatment of this rare but aggressive tumor. Expression of components of the TRAIL pathway was analyzed in tumor specimens and isolated primary tumor cells at the protein level. Cells were treated with TRAIL, Bortezomib, and a combination thereof, and apoptosis induction was quantified. Clonogenicity assays were performed to elucidate the long-term effect of this treatment. Despite expressing all components of the TRAIL pathway, freshly isolated primary esthesioneuroblastoma cells were completely resistant to TRAIL-induced apoptosis. They could, however, be very efficiently sensitized by subtoxic doses of Bortezomib. The influence of Bortezomib on the TRAIL pathway was analyzed and showed upregulation of TRAIL death receptor expression, enhancement of the TRAIL death-inducing signaling complex (DISC), and downregulation of anti-apoptotic proteins of the TRAIL pathway. Of clinical relevance, TRAIL-resistant primary tumor cells could be repeatedly sensitized by Bortezomib, providing the basis for repeated clinical application schedules. This is the first report on the highly synergistic induction of apoptosis in primary esthesioneuroblastoma cells by Bortezomib and TRAIL. This combination, therefore, represents a promising novel therapeutic option for esthesioneuroblastoma.

Assessment of neuropsychological parameters and quality of life to evaluate outcome in patients with surgically treated supratentorial meningiomas.

OBJECTIVE: According to current outcomes research programs, assessment of a broad spectrum of parameters, including quality of life indices, is required to adequately reflect the results of a given treatment. We performed a comprehensive evaluation in patients after supratentorial meningioma surgery in a retrospective study. METHODS: In 91 consecutive patients, outcome was assessed in individual sessions in patients' homes an average of 15 months (standard deviation, +/- 3.6 months) after surgery. The survey included tests of cognitive performance, coping strategies, satisfaction with life, and a structured interview. RESULTS: We found a significant negative correlation between patient age and cognitive performance (P < 0.001), with a major decline beginning at the age of 55 years. Despite normal cognitive performance, 73% of younger patients (younger than 55 years) compared with 20% of older patients (P < 0.001) were not satisfied with life. As a major problem, 68% of younger patients described an inability to accept having this severe disease as a young person. Patients living as singles had a higher frequency of depressive coping (P < 0.05) and less satisfaction with life (P < 0.05). CONCLUSION: Comprehensive evaluation after meningioma surgery is required to prevent poor long-term results after apparently successful surgery. In our study, tests and structured interviews revealed different aspects, especially concerning patient age. Because demographic variables clearly influenced satisfaction with life, evaluation of quality of life must account for these factors to improve comparison of different studies. However, prospective studies with larger cohorts and control groups are required to prove our hypotheses.

Genome-wide genetic characterization of an atypical meningioma by single-nucleotide polymorphism array-based mapping and classical cytogenetics.

Most meningiomas, accounting for about 20% of intracranial tumors, can be cured by surgical removal. Yet, 8-22% of these tumors are classified as atypical or anaplastic (WHO grade II or III, respectively) presenting with a more aggressive behavior and a high relapse rate. We analyzed genomic alterations of an atypical meningioma using high-density single nucleotide polymorphism arrays (SNP-A) karyotyping combined with GTG-banding, multicolor fluorescence in situ hybridization (M-FISH), and locus-specific FISH. In accordance to recent studies applying SNP-A karyotyping in different malignancies we found that genomic lesions are present at a higher frequency than predicted by traditional cytogenetics. Most of these aberrations have not been described before. Additionally, we unveiled loss of heterozygosity (LOH) without copy number changes on chromosome regions 1p31.1, 2p16.1, 2q23.3, 6q14.1, 6q21, 9p21.1, 10q21.1, and 14q23.3, suggesting partial uniparental disomy (UPD). UPDs are currently considered to play an important role in the initiation and progression of different malignancies. Furthermore, we detected two de novo reciprocal translocations, t(8;19)(q24;q13) and t(10;16)(q22;q12.1). While GTG-banding and M-FISH data suggested balanced translocations, SNP-A analysis clearly demonstrated imbalances in the same region.

Cytogenetic and molecular biological characterization of an adult medulloblastoma.

Medulloblastoma is a malignant invasive embryonal tumor, occurring in children mainly. It is rare in adults (<1% of adult brain tumors), and so comprehensive cytogenetic and molecular biological data on adult medulloblastomas are very limited. Conventional therapies provide disappointing long-term disease control, and new therapeutic options are being tested. We performed comprehensive cytogenetic analyses of an adult medulloblastoma, WHO grade IV, using trypsin-Giemsa staining (GTG-banding), multicolor fluorescence in situ hybridization (M-FISH), and locus-specific FISH, complemented by molecular karyotyping using high-density single nucleotide polymorphism (SNP) arrays. GTG-banding of 25 metaphases revealed 31 structural chromosomal aberrations, predominantly located on chromosomes 4q, 9q, 10q, 11p, and 20q, which were confirmed by M-FISH. Two novel, so far not described translocations were found: t(4;11)(q25;p15) and t(9;20)(p23;p12). GTG-banding, locus-specific FISH, and M-FISH detected numerical changes of chromosomes 8, 14, 18, 19, 20, 21, and 22. Molecular karyotyping by SNP array confirmed chromosomal changes -2p, -10q, -16q, and -Xq and revealed de novo partial uniparental disomy 1q and 9q. Applying an upcoming therapeutic approach, we found that primary medulloblastoma cells were resistant to TRAIL, a novel anticancer cytokine, but could be efficiently sensitized by cotreatment with the proteasome inhibitor bortezomib. Bortezomib-TRAIL cotreatment may serve as a powerful therapeutic option for medulloblastoma patients.