Distribution of segmental chromosomal alterations in neuroblastoma.

BACKGROUND: Neuroblastoma (NB) is a heterogeneous tumor with extremely diverse prognosis according to clinical and genetic factors such as specific combinations of chromosomal imbalances. METHODS: Molecular karyotyping data from a national neuroblastic tumor database of 155 NB samples were analyzed and related to clinical data. RESULTS: Segmental chromosomal alterations (SCA) were detected in 102 NB, whereas 45 only displayed numerical alterations. Incidence of SCA was higher in stage M (92%) and MYCN amplified (MNA) NB (96%). Presence of SCA was associated with older age, especially 1q gain and 3p deletion. 96% of the deaths were observed in the SCA group and 85% of the relapsed NB contained SCA. The alteration most commonly associated with a higher number of other segmental rearrangements was 11q deletion, followed by 4p deletion. Whole-chromosome 19 gain was associated with lower stages, absence of SCA and better outcome. CONCLUSIONS: SCA are not randomly distributed and are concentrated on recurrent chromosomes. The most frequently affected chromosomes identify prognostic factors in specific risk groups. SCA are associated with older age and MNA. We have identified a small subset of patients with better outcome that share whole-chromosome 19 numeric gain, suggesting its use as a prognostic biomarker in NB.

Precision medicine in Ewing sarcoma: a translational point of view.

Ewing sarcoma is a rare tumor that arises in bones of children and teenagers but, in 15% of the patients it is presented as a primary soft tissue tumor. Balanced reciprocal chimeric translocation t(11;22)(q24;q12), which encodes an oncogenic protein fusion (EWSR1/FLI1), is the most generalized and characteristic molecular event. Using conventional treatments, (chemotherapy, surgery and radiotherapy) long-term overall survival rate is 30% for patients with disseminated disease and 65-75% for patients with localized tumors. Urgent new effective drug development is a challenge. This review summarizes the preclinical and clinical investigational knowledge about prognostic and targetable biomarkers in Ewing sarcoma, finally suggesting a workflow for precision medicine committees.

Li-Fraumeni syndrome heterogeneity.

Clinical variability is commonly seen in Li-Fraumeni syndrome. Phenotypic heterogeneity is present among different families affected by the same pathogenic variant in TP53 gene and among members of the same family. However, causes of this huge clinical spectrum have not been studied in depth. TP53 type mutation, polymorphic variants in TP53 gene or in TP53-related genes, copy number variations in particular regions, and/or epigenetic deregulation of TP53 expression might be responsible for clinical heterogeneity. In this review, recent advances in the understanding of genetic and epigenetic aspects influencing Li-Fraumeni phenotype are discussed.

Retinoblastoma: towards an earlier diagnosis. / Retinoblastoma: hacia un diagnóstico más precoz.

OBJECTIVES: The number of enucleations and visual sequels due to retinoblastoma is high. The aim of this study was to evaluate the different diagnostic aspects and propose strategies that might improve the clinical management of this condition. METHOD: A retrospective study was conducted on 38 patients with retinoblastoma studied genetically (29 unilateral, 9 bilateral). The evaluation included: age of onset, clinical signs, and time since onset, number of enucleations, time to diagnosis, and survival at 5 years. RESULTS: Leukocoria was the main clinical sign (present in 90% of cases). The mean diagnostic delay was 3.2 months. Among the unilateral cases, the eyes were enucleated in 76%, and 55% in the bilateral forms. Only one death was found among the 25 patients followed-up for at least 5 years. CONCLUSIONS: Retinoblastoma diagnostic and treatment strategies need to be updated. Good coordination between paediatricians and ophthalmologists is essential for this. Its management in reference centres, which have the necessary technology and experience, should contribute to increase the rate of organ preservation.

Behavioral changes in models of chemoconvulsant-induced epilepsy: A review.

Epilepsy is one of the most common neurological disorders in the general population and affects over 50 million people worldwide. Epilepsy is characterized by the presence of spontaneous recurrent seizures as a result of sudden and abnormal electrical activity in specific areas of the cerebral cortex. However, this condition encompasses much more than simply the presence of seizures. Cognitive problems and behavioral impairments are also frequent actors, as well as mood disorders. These must be precisely described in order to develop more successful pharmacological, or even behavioral, treatments. We review some of the fundamental behavioral experimental rodent protocols that have recently been applied to the study of behavioral impairments in epilepsy, particularly in epilepsy modeled by different chemoconvulsants, such as pilocarpine or kainic acid. These experimental protocols are classified into two categories: Tests designed for studying emotional factors, and those designed for studying cognitive impairments and social behavior. Behavioral impairments and adaptations identified by the use of these procedures are described.

Epigenetic alterations in disseminated neuroblastoma tumour cells: influence of TMS1 gene hypermethylation in relapse risk in NB patients.

PURPOSE: Most neuroblastoma patients over 18 months of age at diagnosis present disseminated disease. The presence of neuroblastoma cells in bone marrow can be used to evaluate the response to treatment. It is possible that alterations in certain tumour cells might confer a selective advantage over tumour dissemination process, and probably be helpful in the clonal selection of tumour-specific cells that could originate metastasis. METHODS: We performed real-time quantitative PCR to identify the presence of disseminated tumour cells in bone marrow samples, and we used MSP to analyse the methylation profile of 20 genes putatively implied in dissemination. RESULTS: We described epigenetic alterations in the methylated status of certain genes in disseminated tumour cells from bone marrow. Those cases with high rate of hypermethylation showed an increased probability of relapse during or after treatment. We found significantly poor prognosis in event-free survival in cases with hypermethylation of TMS1, MGMT and RARbeta2 genes. CONCLUSION: We could not confirm the presence of a specific methylation profile in disseminated neuroblastoma tumour cells, but a high accumulation of epigenetic events in those cells is associated with a high risk of relapse, independently of MYCN amplification.

Noise level analysis in buffer rod geometries for ultrasonic sensors.

This work presents an ultrasonic sensor for on-line batter monitoring with low-noise design considerations. The density and the compressibility of the batter vary as a function of mixing time and are strongly related to the quality of the final product. Traditionally, a batter sample of a fixed volume is removed and weighted in order to determine its density. This is a time consuming process. Benefits to the industry of on-line measuring techniques include better control of product quality, improving processing efficiencies and reduction in wastage. In this paper low-noise design considerations are accounted for an ultrasonic sensor based on a piezoceramic disk mounted between two reference buffer rods of acrylic resin to measure the acoustic impedance of the batter. Measuring the acoustic impedance changes of the batter its compressibility and density can be monitored. Spurious echoes generated at different parts of the buffer rods boundary strongly affect accuracy and reliability of the measurements, and are considered as noise. The influence of buffer rods geometry on noise level is studied using simulations and afterwards justified experimentally. Design aspects such as buffer rods length and radius, piezoceramic disk frequency and radius are discussed and their influence on noise level is shown. Finally, strategies for optimum geometry design of the ultrasonic sensor are given.

Effects of severe depression on TOMM performance among disability-seeking outpatients.

The purpose of this study is to examine the effects of severe depression on the Test of Memory Malingering (TOMM). The present study examined whether 20 participants with high levels of depression, as measured by the Beck Depression Inventory 2nd Edition (BDI-II) and with current diagnoses of Major Depressive Disorder, would perform significantly worse on the TOMM than a control group. The results showed that the depressed and control groups did not have significant mean group differences on TOMM performance. Of the 20 depressed participants, only 2 on Trial 2 and 1 on the Retention Trial scored below the cutoff of 45, while none of the control participants performed in this range. The potential ameliorating effects of medications on the performance of the depressed group are discussed. The results indicate that the TOMM can be used with even severely depressed participants with only slight caution.