Liponeurocitoma del ventrículo lateral izquierdo. Revisión del primer caso descrito en España y análisis de la bibliografía / Liponeurocytoma in the left lateral ventricle. Presentation of the first case reported in Spain and literature review

El liponeurocitoma supratentorial es un tumor excepcional, de predominio en varones jóvenes. Su localización habitual son los ventrículos laterales, siendo excepcional la afectación del iii ventrículo. Se define como un tumor neuronoglial, de bajo grado, con áreas de lipomatosis asociada. La manifestación clínica más frecuente es la derivada de la aparición de hidrocefalia e hipertensión intracraneal secundaria. Presentamos el primer caso descrito en España de esta estirpe tumoral y uno de los pocos presentados, hasta la fecha, en las bases bibliográficas. Se describe el caso de un varón de 33 años de edad, afectado de clínica sensitiva crural y cefalea de reciente inicio. El estudio radiológico mostró la presencia de una gran tumoración supratentorial, intraventricular, multiquística, heterogénea, con áreas de lipomatosis asociada. El paciente fue intervenido, consiguiéndose la exéresis tumoral completa. El diagnóstico definitivo fue de liponeurocitoma supratentorial. La presencia de una tumoración intraventricular supratentorial, con áreas de degeneración grasa, debe obligar a considerar, dentro del diagnóstico diferencial, este tipo de tumor. La resección tumoral completa se considera el tratamiento de elección

Supratentorial liponeurocytoma is a rare tumor, predominatly appearing in young males. It most commonly affects the lateral ventricles, with involvement of the third ventricle being exceptional. It is defined as a low-grade neuroglial tumor, with areas of associated lipomatosis. The most common clinical manifestation is that resulting from the presence of secondary intracranial hypertension and hydrocephalus. We present the first case reported in Spain of this tumor type and one of the few appearing in the literature so far. We report the case of a 33-year-old male patient, suffering from crural sensitive sympoms and recent onset headache. The radiographic study revealed the presence of a large supratentorial tumor; intraventricular, multicystic, heterogeneous and with areas of associated lipomatosis. The patient underwent surgery and complete tumor resection was achieved. The definitive diagnosis was of supratentorial liponeurocytoma. The presence of a supratentorial intraventricular tumor with areas of fatty degeneration should lead us to consider this type of tumor in the differential diagnosis. Complete tumor resection is considered to be the treatment of choice

[Liponeurocytoma in the left lateral ventricle. Presentation of the first case reported in Spain and literature review]. / Liponeurocitoma del ventrículo lateral izquierdo. Revisión del primer caso descrito en España y análisis de la bibliografía.

Supratentorial liponeurocytoma is a rare tumor, predominantly appearing in young males. It most commonly affects the lateral ventricles, with involvement of the third ventricle being exceptional. It is defined as a low-grade neuroglial tumor, with areas of associated lipomatosis. The most common clinical manifestation is that resulting from the presence of secondary intracranial hypertension and hydrocephalus. We present the first case reported in Spain of this tumor type and one of the few appearing in the literature so far. We report the case of a 33-year-old male patient, suffering from crural sensitive symptoms and recent onset headache. The radiographic study revealed the presence of a large supratentorial tumor; intraventricular, multicystic, heterogeneous and with areas of associated lipomatosis. The patient underwent surgery and complete tumor resection was achieved. The definitive diagnosis was of supratentorial liponeurocytoma. The presence of a supratentorial intraventricular tumor with areas of fatty degeneration should lead us to consider this type of tumor in the differential diagnosis. Complete tumor resection is considered to be the treatment of choice.

Differential expression profiling analyses identifies downregulation of 1p, 6q, and 14q genes and overexpression of 6p histone cluster 1 genes as markers of recurrence in meningiomas.

The majority of meningiomas are probably benign but a number of tumors display considerable histological and/or clinical aggressivity, sometimes with unexpectedly high recurrence rates after radical removal. Understanding the potential behavior of these tumors in individual patients is critical for rational therapeutic decision-making. This study aimed to identify gene expression profiles and candidate markers associated with original and recurrent meningiomas. Unsupervised hierarchical clustering of the samples confirmed 2 main groups of meningiomas with distinct clinical behaviors. The gene expression profiling study identified genes and pathways potentially associated with meningioma recurrence, revealing an overall lower level of gene expression. The differential gene expression profiling analyses of original and recurrent meningiomas identified 425 known genes and expressed sequence tags related to meningioma recurrence, with SFRP1 (8p12), TMEM30B (14q23), and CTGF (6q23) showing the most disparate expression. Most of the differentially expressed genes were located at 1p, 6q, and 14q and were underexpressed in recurrences. Loss of such chromosomal regions has previously been associated with a higher risk of meningioma recurrence or malignant progression. Thus, at these locations, we propose the existence of novel candidate genes that could be involved in meningioma recurrence. In addition, the overexpression of genes of histone cluster 1 (6p) in recurrent meningiomas is reported here for the first time. Finally, the altered genes related to meningioma recurrence are involved in pathways such as Notch, TGFß, and Wnt, as described previously, and in other pathways such as cell cycle, oxidative phosphorylation, PPAR, and PDGF, not related before to meningioma recurrence.

Microarray-based comparative genomic hybridization (array-CGH) as a useful tool for identifying genes involved in Glioblastoma (GB).

Alterations in the genome that lead to changes in DNA sequence copy number are a characteristic of Glioblastomas (GBs). Microarray-based comparative genomic hybridization (array-CGH) is a high-throughput technology that allows the hybridization of genomic DNA onto conventional cDNA microarrays, normally used in expression profiling, to analyze genomic copy number imbalances. In this way, thousands of genes can be reviewed in a high resolution analysis to define amplicons and to identify? candidate genes showing recurrent genomic copy number changes in GB tumors.

Novel genomic alterations and mechanisms associated with tumor progression in oligodendroglioma and mixed oligoastrocytoma.

Combined 1p/19q deletions are very prevalent in oligodendrogliomas (OGs) and, to a lesser extent, in oligoastrocytomas (OAs). These losses are associated with responsiveness to therapy. Using array-based comparative genomic hybridization, we screened for recurrent genomic alterations in OG and oligoastrocytoma subtypes on chromosome 19. Concomitant 1p/19q loss was detected in most of the tumors with allelic loss, but array-based comparative genomic hybridization revealed some tumors to have unrelated 1p/19q arm losses, suggesting alternative mechanisms of loss to that related to the reported t(1;19) translocation. Analyses of 1p/19q loss by fluorescence in situ hybridization and loss of heterozygosity assays and correlations of genomic data with the Ki-67 proliferation marker were also performed. Four 1q (or 19p) and 2 1p (or 19q) fluorescence in situ hybridization probe signals together with homozygosity of the 1p/19q microsatellites suggested a hypothetical mechanism of genome duplication consecutive to the loss of the derivative chromosome der(1p;19q) from the t(1;19)(1q;19p) translocation. This genome duplication was frequent in high-grade OGs and was strongly correlated with Ki-67 expression; thus, it could be related to tumor progression. Finally, in addition to the frequent 1p/19q loss, we report a novel 17q amplified region in OGs with BIRC5 as one of the possible candidate target genes of the amplicon.

Worse outcome in primary glioblastoma multiforme with concurrent epidermal growth factor receptor and p53 alteration.

Primary glioblastoma multiforme (GBM), in contrast with secondary GBM, has been associated with the presence of EGFR amplification and absence of p53 mutation. In this study, we analyzed relevant molecular and clinical variables in 194 primary GBMs and tested them for survival analysis. Although most of the tumors showed a mutually exclusive pattern, concurrent alterations of EGFR and p53 were detected. Survival analysis of CDK4 amplification revealed a highly significant association with a worse clinical outcome (P = .01), whereas MDM2, CDK6, PTEN, and p21 were not associated with patient survival. Multivariate analysis including the significant clinical and molecular variables revealed CDK4 amplification, age, and radiotherapy to be markers with independent prognostic value. In addition, the primary GBM tumors showing simultaneous EGFR and p53 alterations were significantly associated with worse survival (P < .01). These results highlight the prognostic value of CDK4 amplification and of simultaneous EGFR-p53 alterations in the clinical outcome of patients with primary GBM.

Identification of survival-related genes of the phosphatidylinositol 3'-kinase signaling pathway in glioblastoma multiforme.

BACKGROUND: Knowledge of the molecular mechanisms involved in the biology of glioblastoma multiforme (GBM) is essential for the identification of candidate prognostic markers, new putative therapeutic targets, and early detection strategies predictive of survival. METHODS: The authors performed expression-profiling analyses in a series of primary GBMs by using complementary DNA microarrays. Validation of putative targets was performed in large series of GBMs by immunohistochemistry on tissue microarrays, real-time quantitative reverse transcription-polymerase chain reaction analysis, and Western blot analysis. RESULTS: The expression signature consisted of 159 up-regulated genes and 186 down-regulated genes. Most of these genes were involved in cell adhesion, signal transduction, cell cycle, apoptosis, and angiogenesis. Among the genes from the molecular signature, annexin 1 (ANXA1) and ubiquitin-specific protease 7 (USP7) were evaluated in wider series of GBMs. ANXA1 analysis carried out in different types of gliomas revealed exclusive overexpression in astrocytomas. Furthermore, survival analysis by using functional clusters of genes related with cancer and glioma biology revealed 7 genes involved in the PI3K-signaling pathway that presented a significant association with clinical outcome. Among these genes, positive expression of BCL2-associated X protein (BAX) was associated significantly with better survival in a larger series of tumors. In addition, activation of the PI3K/Akt pathway was demonstrated in this set of GBMs. CONCLUSIONS: The authors concluded that there is a significant role for PI3K pathway survival-related genes in patients with GBM, and putative prognostic markers associated with glioma tumorigenesis were identified. The detailed study of these candidate genes and the molecular pathways regulating PI3K activation reveal that they are promising targets for the clinical management of patients with glioma.

Identification of novel candidate target genes in amplicons of Glioblastoma multiforme tumors detected by expression and CGH microarray profiling.

BACKGROUND: Conventional cytogenetic and comparative genomic hybridization (CGH) studies in brain malignancies have shown that glioblastoma multiforme (GBM) is characterized by complex structural and numerical alterations. However, the limited resolution of these techniques has precluded the precise identification of detailed specific gene copy number alterations. RESULTS: We performed a genome-wide survey of gene copy number changes in 20 primary GBMs by CGH on cDNA microarrays. A novel amplicon at 4p15, and previously uncharacterized amplicons at 13q32-34 and 1q32 were detected and are analyzed here. These amplicons contained amplified genes not previously reported. Other amplified regions containing well-known oncogenes in GBMs were also detected at 7p12 (EGFR), 7q21 (CDK6), 4q12 (PDGFRA), and 12q13-15 (MDM2 and CDK4). In order to identify the putative target genes of the amplifications, and to determine the changes in gene expression levels associated with copy number change events, we carried out parallel gene expression profiling analyses using the same cDNA microarrays. We detected overexpression of the novel amplified genes SLA/LP and STIM2 (4p15), and TNFSF13B and COL4A2 (13q32-34). Some of the candidate target genes of amplification (EGFR, CDK6, MDM2, CDK4, and TNFSF13B) were tested in an independent set of 111 primary GBMs by using FISH and immunohistological assays. The novel candidate 13q-amplification target TNFSF13B was amplified in 8% of the tumors, and showed protein expression in 20% of the GBMs. CONCLUSION: This high-resolution analysis allowed us to propose novel candidate target genes such as STIM2 at 4p15, and TNFSF13B or COL4A2 at 13q32-34 that could potentially contribute to the pathogenesis of these tumors and which would require futher investigations. We showed that overexpression of the amplified genes could be attributable to gene dosage and speculate that deregulation of those genes could be important in the development and progression of GBM. Our findings highlight the important influence in GBM of signaling pathways such as the PI3K/AKT, consistent with the invasive features of this tumor.