Myelodysplastic syndromes (MDS) are myeloid malignancies characterized by ineffective hematopoiesis, dysplasia, peripheral cytopenia and increased risk of progression to acute myeloid leukemia. Refractory cytopenia of childhood (RCC) is the most common subtype of pediatric MDS and has overlapping clinical features with viral infections and autoimmune disorders. Mutations in TET2 gene are found in about 20–25% of adult MDS and are associated with a decrease in 5-hydroxymethylcytosine (5-hmC) content. TET2 deregulation and its malignant potential were reported in adult but not in pediatric MDS. We evaluated the gene expression and the presence of mutations in TET2 gene in 19 patients with RCC. TET2expression level was correlated with 5-hmC amount in DNA and possible regulatory epigenetic mechanisms. One out of 19 pediatric patients with RCC was a carrier of a TET2 mutation. TET2 expression and 5-hmC levels were decreased in patients when compared to a disease-free group. Lower expression was not associated to the presence of mutation or with the status of promoter methylation, but a significant correlation with microRNA-22 expression was found. These findings suggested that TET2 downregulation and low levels of 5-hmC are inversely related to miR-22 expression. The existence of a regulatory loop between microRNA-22 and TET2 may play a role in MDS pathogenesis.
Neuroblastoma
Neuroblastoma starts in early forms of nerve cells found in a developing embryo or fetus. About 6% of childhood cancers are neuroblastomas. This type of cancer develops in infants and young children. It is rarely found in children older than 10. The tumor can start anywhere but usually starts in the belly (abdomen) where it is noticed as swelling. It can also cause bone pain and fever.
Introduction
Clinical heterogeneity has been thought to be a norm rather than an exception in many diseases -which indicates how different deregulated genetic pathways may lead to the same disease. Although many of previous studies[1-19] on the disease spectrum in pediatric AML/ALL and brain tumors have considerably focused on characterization of disease progression and targeted therapy, little has been known how abnormal patterns identified by super machinery Seq-based platforms explicitly work at cellular, molecular, organism al and functional level in personalized medicine as the causal and consequent effects. A better understanding of each part of genetic or genomic susceptibility and their ensemble contributors such as gene fusions and disease specific epigenetic modification will enable to more precisely uncover the complexity of pediatric tumorigenesis and target novel treatments.