Subependymal giant cell astrocytomas are characterized by mTORC1 hyperactivation, a very low somatic mutation rate, and a unique gene expression profile

Subependymal giant-cell astrocytomas (SEGAs) are slow-growing brain tumors that are a hallmark feature seen in 5–10% of patients with Tuberous Sclerosis Complex (TSC). Though histologically benign, they can cause serious neurologic symptoms, leading to death if untreated. SEGAs consistently show biallelic loss of TSC1 or TSC2. Herein, we aimed to define other somatic events beyond TSC1/TSC2 loss and identify potential transcriptional drivers that contribute to SEGA formation. Paired tumor-normal whole-exome sequencing was performed on 21 resected SEGAs from 20 TSC patients. Pathogenic variants in TSC1/TSC2 were identified in 19/21 (90%) SEGAs. Copy neutral loss of heterozygosity (size range: 2.2–46 Mb) was seen in 76% (16/21) of SEGAs (44% chr9q and 56% chr16p). An average of 1.4 other somatic variants (range 0–7) per tumor were identified, unlikely of pathogenic significance. Whole transcriptome RNA-sequencing analyses revealed 190 common differentially expressed genes in SEGA (n = 16, 13 from a prior study) in pairwise comparison to each of: low grade diffuse gliomas (n = 530) and glioblastoma (n = 171) from The Cancer Genome Atlas (TCGA) consortium, ganglioglioma (n = 10), TSC cortical tubers (n = 15), and multiple normal tissues. Among these, homeobox transcription factors (TFs) HMX3, HMX2, VAX1, SIX3; and TFs IRF6 and EOMES were all expressed >12-fold higher in SEGAs (FDR/q-value < 0.05). Immunohistochemistry supported the specificity of IRF6, VAX1, SIX3 for SEGAs in comparison to other tumor entities and normal brain. We conclude that SEGAs have an extremely low somatic mutation rate, suggesting that TSC1/TSC2 loss is sufficient to drive tumor growth. The unique and highly expressed SEGA-specific TFs likely reflect the neuroepithelial cell of origin, and may also contribute to the transcriptional and epigenetic state that enables SEGA growth following two-hit loss of TSC1 or TSC2 and mTORC1 activation

Diet quality of preschool children and maternal perceptions/misperceptions: The GENESIS study

Objectives: To quantify maternal perceptions regarding the quality of their child&apos;s diet, and to identify factors associated with misperceptions. Study design: A representative sample of 2287 children aged 2-5 years from a cross-sectional study (GENESIS study) was used. Methods: Maternal perceptions of the quality of their child&apos;s diet, child&apos;s and mother&apos;s anthropometric characteristics, and other characteristics (i.e. socio-demographic and lifestyle) were recorded. The actual quality of each child&apos;s diet was estimated using the Healthy Eating Index (HEI) score. Results: Based on the HEI score, 18.3% of participants had a &apos;poor&apos; diet, 81.5% had a diet which &apos;needs improvement&apos; and only 0.2% had a &apos;good&apos; diet. Almost 83% of mothers overestimated the quality of their child&apos;s diet. The overestimation rate was 86% among mothers who declared that they choose their child&apos;s food based on what they consider to be healthy, and 72% among those who reported that other factors play the predominant role in food choices for their child (P &lt; 0.001). Moreover, total energy intake as well as the intake of fruits, grains, vegetables, meat and milk was significantly higher among children whose mothers overestimated the quality of their diet. Conclusion: The vast majority of mothers overestimate the quality of their child&apos;s diet. Given that maternal perceptions regarding the quality of their child&apos;s diet are likely to be one of the predominant factors determining the child&apos;s food intake, health professionals should make mothers aware of the existence of particular dietary recommendations that their children should meet in order to eat a healthy diet. © 2009 The Royal Society for Public Health

Fiber intake and childhood appendicitis

In order to investigate the possible role of fiber in the etiology of acute appendicitis, 203 consecutive appendectomized children with histologically proved appendicitis and 1922 controls were studied by the diet history method. Statistics were performed by multivariate analysis of variance, discriminant analysis and χ2. Appendectomized children had statistically significant lower mean daily intake of fiber (17.4 g versus 20.4 g, P &amp;lt; 0.001) including all fiber fractions: cellulose, uronic acid, pentose, exose and lignin. No statistical difference was found for energy, protein, carbohydrate and fat intake. Discriminant analysis proved that only cellulose and exose are independently correlated to appendicitis and lower fiber intake is thought to be the cause in 70% of the cases. Recurrent abdominal pain, chronic constipation and positive family history of appendectomy were more frequent in appendectomized children (P &amp;lt; 0.001). This study gives evidence that low fiber intake could play an important role in the pathogenesis of appendicitis

Obesity and television watching in preschoolers in greece: The genesis study

The aim of the current work was to evaluate the effect of preschoolers&apos; television (TV) watching time on the prevalence of obesity even after controlling for their total energy intake and their physical activity status. A representative sample of 2,374 Greek children aged 1-5 years was examined (Growth, Exercise and Nutrition Epidemiological Study in preSchoolers, GENESIS study). Children&apos;s TV watching time on a usual weekday and at a usual weekend was recorded. The overall mean of children&apos;s TV viewing time was 1.32 h/day. The majority of participants (74.0%) spent 2 h/day watching TV whereas only 3.1% spent 4 h/day in front of a TV set. Overall, 65.2% of participants were normal weight, 17.2% were overweight, and the rest 17.6% were obese. The prevalence of obesity was significantly higher among those with TV viewing time 2 h/day (21.7%) compared to those watching TV 2 h/day (16.1%, P = 0.003). TV viewing time remained significantly associated with the likelihood of being obese even after controlling for potential confounders (i.e., socio demographic and other characteristics and physical activity status) only among children aged 3-5 years. However, further adjusting for children&apos;s total energy intake revealed that the association between the TV viewing time and the probability of being obese was no longer statistically significant. On the other hand, physical activity status continued to be an independent factor of being obese. The current findings support the hypothesis that the effect of TV viewing time on childhood obesity is independent of physical activity status and may be attributed to the increased total energy intake during TV watching

Erratum: An interstitial deletion at 8q23.1-q24.12 associated with Langer-Giedion syndrome/Trichorhinophalangeal syndrome (TRPS) type II and Cornelia de Lange syndrome 4 (Molecular Cytogenetics (2015) 8:64 DOI: 10.1186/s13039-015-0169-9)

The original version of this article [1] unfortunately contained a mistake. In the author list, the surname of author Krinio Giannikou was incorrectly spelled. The original article has now been updated with the correct spelling. © 2015 Selenti et al

Further delineation of novel 1p36 rearrangements by array-CGH analysis: Narrowing the breakpoints and clarifying the &quot;extended&quot; phenotype

High resolution oligonucleotide array Comparative Genome Hybridization technology (array-CGH) has greatly assisted the recognition of the 1p36 contiguous gene deletion syndrome. The 1p36 deletion syndrome is considered to be one of the most common subtelomeric microdeletion syndromes and has an incidence of ~. 1 in 5000 live births, while respectively the &quot;pure&quot; 1p36 microduplication has not been reported so far.We present seven new patients who were referred for genetic evaluation due to Developmental Delay (DD), Mental Retardation (MR), and distinct dysmorphic features. They all had a wide phenotypic spectrum. In all cases previous standard karyotypes were negative. Array-CGH analysis revealed five patients with interstitial 1p36 microdeletion (four . de novo and one maternal) and two patients with . de novo reciprocal duplication of different sizes. These were the first reported &quot;pure&quot; 1p36 microduplication cases so far. Three of our patients carrying the 1p36 microdeletion syndrome were also found to have additional pathogenetic aberrations. These findings (del 3q27.1; del 4q21.22-q22.1; del 16p13.3; dup 21q21.2-q21.3; del Xp22.12) might contribute to the patients&apos; severe phenotype, acting as additional modifiers of their clinical manifestations. We review and compare the clinical and array-CGH findings of our patients to previously reported cases with the aim of clearly delineating more accurate genotype-phenotype correlations for the 1p36 syndrome that could allow for a more precise prognosis. © 2012 Elsevier B.V

Array comparative genomic hybridization as a clinical diagnostic tool in syndromic and nonsyndromic congenital heart disease

Background:Congenital heart diseases (CHDs) are often associated with other congenital anomalies, dysmorphic features, and developmental delay, and only a few cases of chromosomal abnormalities are detected by conventional cytogenetic techniques. The microarray comparative genomic hybridization (CGH) analysis allows the identification of submicroscopic genomic rearrangements.Methods: During the past 3 y, 55 of 330 patients referred for array CGH had CHD of unknown etiology plus at least one additional indication of abnormal chromosomal phenotype. High-resolution 1 × 244K or 4 × 180K Agilent arrays were used in this study (average resolution 7-13 kb).Results:Copy-number variations were detected in 37 of 55 patients, and in 29 of 37 patients there were genes that have been associated with CHD. All 37 patients had at least one additional phenotypic abnormality: 30 of 37 had one or more other congenital anomalies, 23 of 37 had dysmorphic features, 16 of 37 had intellectual disability, 13 of 37 had abnormal magnetic resonance imaging, 10 of 37 had hypotonia, and 7 of 37 had seizures. In 9 of 55 patients, unexpected genomic rearrangements in relation to their phenotype were identified.Conclusion:In patients with CHD and at least one additional indication of abnormal chromosomal phenotype, array CGH analysis could detect possible submicroscopic chromosomal abnormalities and provide proper genetic counseling. Copyright © 2013 International Pediatric Research Foundation, Inc

New miRNA profiles accurately distinguish renal cell carcinomas and upper tract urothelial carcinomas from the normal kidney

Background: Upper tract urothelial carcinomas (UT-UC) can invade the pelvicalyceal system making differential diagnosis of the various histologically distinct renal cell carcinoma (RCC) subtypes and UT-UC, difficult. Correct diagnosis is critical for determining appropriate surgery and post-surgical treatments. We aimed to identify microRNA (miRNA) signatures that can accurately distinguish the most prevalent RCC subtypes and UT-UC form the normal kidney. Methods and Findings: miRNA profiling was performed on FFPE tissue sections from RCC and UT-UC and normal kidney and 434 miRNAs were significantly deregulated in cancerous vs. the normal tissue. Hierarchical clustering distinguished UT-UCs from RCCs and classified the various RCC subtypes among them. qRT-PCR validated the deregulated expression profile for the majority of the miRNAs and ROC analysis revealed their capability to discriminate between tumour and normal kidney. An independent cohort of freshly frozen RCC and UT-UC samples was used to validate the deregulated miRNAs with the best discriminatory ability (AUC&gt;0.8, p&lt;0.001). Many of them were located within cytogenetic regions that were previously reported to be significantly aberrated. miRNA targets were predicted using the miRWalk algorithm and ingenuity pathway analysis identified the canonical pathways and curated networks of the deregulated miRNAs. Using the miRWalk algorithm, we further identified the top anti-correlated mRNA/miRNA pairs, between the deregulated miRNAs from our study and the top co-deregulated mRNAs among 5 independent ccRCC GEO datasets. The AB8/13 undifferentiated podocyte cells were used for functional assays using luciferase reporter constructs and the developmental transcription factor TFCP2L1 was proved to be a true target of miR-489, which was the second most upregulated miRNA in ccRCC. Conclusions: We identified novel miRNAs specific for each RCC subtype and UT-UC, we investigated their putative targets, the networks and pathways in which they participate and we functionally verified the true targets of the top deregulated miRNAs. © 2014 Zaravinos et al