Isocitrate Dehydrogenase 1 and 2 Mutations in Pediatric Neuroblastoma Patients.

Objective: Neuroblastoma is one of the common tumors of childhood. The demonstration of new factors such as isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) mutations will be important in the diagnosis and treatment. IDH1 and IDH2 mutations have been found in many types of cancer, such as malignant gliomas, acute myeloid leukemias, chondrosarcoma, and thyroid carcinoma. This study aimed to investigate the presence of IDH1 or IDH2 mutations in patients with neuroblastoma and to determine whether these mutations were different in terms of age, clinical findings, and response to treatment. Methods: Biopsy specimens of 25 patients with pediatric neuroblastoma patients were evaluated for IDH mutations. The clinical and laboratory features of the patients with/without mutation were retrospectively analyzed from a hospital database. Results: A total of 25 patients for whom genetic analysis could be performed were included in the study (60% male, n=15). The mean age was 32.2±25.9 months (3 days-96 months). IDH1 mutation was detected in 8 (32%) and IDH2 mutations in 5 (20%) patients. These mutations showed no statistically significant relationship with age, tumor localization, laboratory results, stage, and prognosis. However, in the case of IDH mutation, patients were diagnosed at the advanced stage. Conclusions: This study demonstrated the relationship between neuroblastoma and IDH mutation for the first time. Because to the fact that the mutation is very heterogeneous, it would be appropriate to conduct a larger series of patients in terms of the impact of the clinical significance of each mutation on the diagnosis and prognosis.

Intrauterine Growth Retardation is a Risk Factor for Anthracycline Toxicity.

BACKGROUND: Anthracycline chemotherapy is used to treat a variety of cancers. However, late cardiac effects of anthracycline chemotherapy, such as subclinical left ventricular dilatation and/or dysfunction, have been observed in more than half of long-term survivors of childhood cancers. A major risk factor for anthracycline cardiotoxicity is intrauterine growth restriction (IUGR). We assessed the significance of IUGR as an important risk factor for late cardiotoxic effects of anthracycline therapy in asymptomatic long-term survivors of childhood cancers. MATERIALS AND METHODS: The study included 61 survivors of childhood cancers. Cardiac functions were prospectively studied using both conventional and non-conventional echocardiographic methods (two-dimensional speckle tracking echocardiography) after completion of the treatment. The patients were divided into two groups based on their birth weights: Group 1 (patients with IUGR) and Group 2 (patients with normal birth weight). RESULTS: Conventional echocardiography revealed a similar and normal range of left ventricle systolic and diastolic functions in both groups. However, global longitudinal and circumferential strain values demonstrated subclinical left ventricular systolic dysfunction in both groups as compared with normal reference strain values. Furthermore, Group 1 patients had significantly lower global longitudinal and circumferential strain and strain rate values than those in Group 2 patients. CONCLUSION: Asymptomatic long-term survivors of childhood cancers with a history of IUGR may have an increased risk of anthracycline cardiotoxicity due to the low content of mitochondrial DNA (mtDNA). IUGR is a risk factor for late anthracycline cardiotoxicity.

The effect of deferasirox on endocrine complications in children with thalassemia.

Endocrine system dysfunctions are the significant complications of excessive iron overload in beta thalassemia patients. The aim of this study was to evaluate the long-term effect of chelation with deferasirox on endocrine complications. The study group consisted of children with beta thalassemia who had been evaluated for the growth and pubertal development, bone metabolism, thyroid/parathyroid functions, glucose metabolism dysfunctions in the department of pediatric hematology of Ankara Diskapi Child Health and Diseases Hematology Oncology Training And Research Hospital between 2009-2011 and reevaluated after deferasirox chelation therapy in 2018. Thirty-one transfusion dependent beta-thalassemia patients were enrolled for the study. Seventeen (54.8%) patients were male and the mean age was 16.9 ± 3.8 (9-23) years. Splenectomy was performed in 11 patients (35.5%). In the initial evaluation, 26 patients (84%) received deferoxamine and/or deferiprone and five (17%) patients received deferasirox as a chelator; in the final evaluation all patients were receiving deferasirox. The mean duration of deferasirox treatment was 5.9 ± 2.02 years (1-10 years). Of the 26 patients who had endocrine complications between 2009-2011, 18 were recovered. In the final evaluation, eight patients (25%) developed new endocrinopathies. The frequency of endocrine complications seen before the deferasirox treatment (83%) was higher than the frequency of complications while receiving deferasirox treatment (25.8%) (p < 0,05). In this study, it was determined that both existing endocrine abnormalities were reduced and recent developed problems were less likely with long-term deferasirox treatment in thalassemia patients.

Epigenotype and phenotype correlations in patients with Beckwith-Wiedemann syndrome.

Bilgin B, Kabaçam S, Taskiran E, Simsek-Kiper PÖ, Alanay Y, Boduroglu K, Utine GE. Epigenotype and phenotype correlations in patients with Beckwith-Wiedemann syndrome. Turk J Pediatr 2018; 60: 506-513. Beckwith-Wiedemann Syndrome (BWS) is one of the most common overgrowth syndromes. Cancer predisposition is an important feature of this clinically heterogeneous syndrome. Patients may have fetal and early childhood overgrowth, hemihyperplasia, macroglossia, facial dysmorphic features, abdominal wall defects, visceromegaly, and anomalies of the heart and the kidneys. Various previous investigations showed that heterogeneous molecular etiology may contribute to clinical variability and that epigenotype-phenotype correlations exist in BWS. This study was performed to detect the molecular etiology in 28 patients with BWS, to search for epigenotype-phenotype correlations and to provide appropriate individualized multidisciplinary approach. Four different molecular etiology groups were determined based on testing for copy number analysis and methylation status at 11p15. Sequencing for CDKN1C mutations were also performed. Groups were compared for various clinical findings. Differences between groups were not statistically significant owing to the small number of patients in individual groups. Statistical studies for epigenotype-phenotype correlations showed significance for only anterior ear lobe creases, visceromegaly and embryonal tumors. Additionally, one interesting patient had a mesenchymal tumor. Anticipating follow-up is clinically important in BWS.