The Transcriptomic Landscape of Pediatric Astrocytoma.

Central nervous system tumors are the most common solid neoplasia during childhood and represent one of the leading causes of cancer-related mortality. Tumors arising from astrocytic cells (astrocytomas) are the most frequently diagnosed, and according to their histological and pathological characteristics, they are classified into four categories. However, an additional layer of molecular classification considering the DNA sequence of the tumorigenesis-associated genes IDH1/2 and H3F3A has recently been incorporated into the classification guidelines. Although mutations in H3F3A are found exclusively in a subtype of grade IV pediatric astrocytoma, mutations in IDH1/2 genes are very rare in children under 14 years of age. The transcriptomic profiles of astrocytoma in adults and children have been extensively studied. However, there is scarce information on these profiles in pediatric populations considering the status of tumorigenesis-associated genes. Therefore, here we report the transcriptomic landscape of the four grades of pediatric astrocytoma by RNA sequencing. We found several well-documented biological functions associated with the misregulated genes in the four grades of astrocytoma, as well as additional biological pathways. Among the four grades of astrocytoma, we found shared misregulated genes that could have implications in tumorigenesis. Finally, we identified a transcriptional signature for almost all grades of astrocytoma that could be used as a transcription-based identification method.

Management experience of pediatric meningioma in a Mexican reference center.

OBJECTIVE: Determine the histopathological and clinical characteristics of patients diagnosed with meningiomas and to establish the frequency of these tumors in the pediatric population Mexican. Determine the NF1/2 frequency in meningioma pediatric. METHODS: Samples from the histopathology file were reviewed, and from the complete clinical file the following patient data was reviewed: age, gender, diagnosis, diagnosis year, surgical resection, location, tumor size, symptoms, and family background. The frequency of NF1/2 in pediatric meningioma was reviewed in literature. RESULTS: Forty-four de novo cases were collected from pediatric patients; 19 were female patients and 25 males. The most frequent histological subtype was transitional meningioma. Of all the cases, 75% had a supratentorial localization and 20% had an extramedullary intrarachidian localization. Some clinical manifestations included seizures, paresis, headache, and visual disturbances. CONCLUSION: There is a low incidence of meningiomas in the pediatric population, more than 70% are Grade I, and they have supratentorial localization.

FAM20C Overview: Classic and Novel Targets, Pathogenic Variants and Raine Syndrome Phenotypes.

FAM20C is a gene coding for a protein kinase that targets S-X-E/pS motifs on different phosphoproteins belonging to diverse tissues. Pathogenic variants of FAM20C are responsible for Raine syndrome (RS), initially described as a lethal and congenital osteosclerotic dysplasia characterized by generalized atherosclerosis with periosteal bone formation, characteristic facial dysmorphisms and intracerebral calcifications. The aim of this review is to give an overview of targets and variants of FAM20C as well as RS aspects. We performed a wide phenotypic review focusing on clinical aspects and differences between all lethal (LRS) and non-lethal (NLRS) reported cases, besides the FAM20C pathogenic variant description for each. As new targets of FAM20C kinase have been identified, we reviewed FAM20C targets and their functions in bone and other tissues, with emphasis on novel targets not previously considered. We found the classic lethal and milder non-lethal phenotypes. The milder phenotype is defined by a large spectrum ranging from osteonecrosis to osteosclerosis with additional congenital defects or intellectual disability in some cases. We discuss our current understanding of FAM20C deficiency, its mechanism in RS through classic FAM20C targets in bone tissue and its potential biological relevance through novel targets in non-bone tissues.

Pediatric ependymoma: GNAO1, ASAH1, IMMT and IPO7 protein expression and 5-year prognosis correlation.

OBJECTIVE: The aim of this work was to evaluate a pediatric ependymoma protein expression that may be useful as a molecular biomarker candidate for prognosis, correlated with clinical features such as age, gender, histopathological grade, ependymal tumor recurrence and patient survival. PATIENTS AND METHODS: Immunohistochemistry assays were performed for GNAO1, ASAH1, IMMT, IPO7, Cyclin D1, P53 and Ki-67 proteins. Kaplan-Meier and Cox analysis were performed for age, gender, histopathological grade, relapse and survival correlation. RESULTS: We found that three proteins correlate with histopathological grade and relapse; two proteins correlate with survival; one protein does not correlate with any clinical feature. CONCLUSION: Our results suggest that, out of the proteins analyzed, five may be considered suitable prognostic biomarkers and one may be considered a predictive biomarker for response to treatment of pediatric ependymoma.

Pediatric pineal germinomas: Epigenetic and genomic approach.

OBJECTIVE: We identify and correlate chromosomal alterations, methylation patterns and gene expression in pediatric pineal germinomas. METHODS: CGH microarray, methylation and gene expression were performed through the Agilent platform. The results were analyzed with MatLab software, MapViewer, DAVID, GeneCards and Hippie. RESULTS: Amplifications were found in 1q24.2, 1q31.3, 2p11.2, 3p22.2, 7p13, 7p15.2, 8p22, 12p13.2, 14q24.3 y 22q12; and deletions were found in 1q21.2, 9p24.1, 10q11.22, 11q11, 15q11.2 and 17q21.31. In the methylation analysis, we observed 10,428 CpG Islands with a modified methylation status that may affect 11,726 genes. We identified 1260 overexpressed genes and 470 underexpressed genes. The genes RUNDC3A, CDC247, CDCA7L, ASAH1, TRA2A, LPL and NPC2 were altered among the three levels. CONCLUSIONS: We identified the 1q24.2 and 1q31.3 amplified regions and the 1q21.3 and 11q11 deleted regions as the most important aims. The genes NPC2 and ASAH1 may play an important role in the development, progression and tumor maintenance. The ASAH1 gene is an ideal candidate to identify drug responses. These genomic and epigenetic studies may help to characterize the formation of pineal germ cell tumors to determine prognostic markers and also to identify shared characteristics in gonadal and extragonadal tumors.

Genomics and epigenetics: A study of ependymomas in pediatric patients.

OBJECTIVE: We identify chromosomal alterations, the methylation pattern and gene expression changes in pediatric ependymomas. METHODS: CGH microarray, methylation and gene expression were performed through the Agilent platform. The results were analyzed with the software MatLab, MapViewer, DAVID, GeneCards and Hippie. RESULTS: Amplification was found in 14q32.33, 2p22.3 and 8p22, and deletion was found in 8p11.23-p11.22 and 1q21.3. We observed 42.387 CpG islands with changes in their methylation pattern, in which we found 272 genes involved in signaling pathways related to carcinogenesis. We found 481 genes with altered expression. The genes IMMT, JHDMD1D, ASAH1, ZWINT, IPO7, GNAO1 and CISD3 were found to be altered among the three levels. CONCLUSION: The 2p22.3, 8p11.23-p11.22 and 14q32.33 regions were identified as the most important; the changes in the methylation pattern related to cell cycle and cancer genes occurred in MIB2, FGF18 and ITIH5. The IPO7, GNAO1 and ASAH1 genes may play a major role in ependymoma development.