Heritable predisposition is an important cause of cancer in children and adolescents. Although a large number of cancer predisposition genes and their associated syndromes and malignancies have already been described, it appears likely that there are more pediatric cancer patients in whom heritable cancer predisposition syndromes have yet to be recognized. In a consensus meeting in the beginning of 2016, we convened experts in Human Genetics and Pediatric Hematology/Oncology to review the available data, to categorize the large amount of information, and to develop recommendations regarding when a cancer predisposition syndrome should be suspected in a young oncology patient. This review summarizes the current knowledge of cancer predisposition syndromes in pediatric oncology and provides essential information on clinical situations in which a childhood cancer predisposition syndrome should be suspected.

SummaryInducing organogenesis in 3D culture is an important aspect of stem cell research. Anterior neural structures have been produced from large embryonic stem cell (ESC) aggregates, but the steps involved in patterning such complex structures have been ill defined, as embryoid bodies typically contained many cell types. Here we show that single mouse ESCs directly embedded in Matrigel or defined synthetic matrices under neural induction conditions can clonally form neuroepithelial cysts containing a single lumen in 3D. Untreated cysts were uniformly dorsal and could be ventralized to floor plate (FP). Retinoic acid posteriorized cysts to cervical levels and induced localize FP formation yielding full patterning along the dorsal/ventral (DV) axis. Correct spatial organization of motor neurons, interneurons, and dorsal interneurons along the DV axis was observed. This system serves as a valuable tool for studying morphogen action in 3D and as a source of patterned spinal cord tissue.

Three-dimensional organoid constructs serve as increasingly widespread in vitro models for development and disease modeling. Current approaches to recreate morphogenetic processes in vitro rely on poorly controllable and ill-defined matrices, thereby largely overlooking the contribution of biochemical and biophysical extracellular matrix (ECM) factors in promoting multicellular growth and reorganization. Here, we show how defined synthetic matrices can be used to explore the role of the ECM in the development of complex 3D neuroepithelial cysts that recapitulate key steps in early neurogenesis. We demonstrate how key ECM parameters are involved in specifying cytoskeleton-mediated symmetry-breaking events that ultimately lead to neural tube-like patterning along the dorsal–ventral (DV) axis. Such synthetic materials serve as valuable tools for studying the discrete action of extrinsic factors in organogenesis, and allow for the discovery of relationships between cytoskeletal mechanobiology and morphogenesis.

BackgroundPediatric follicular lymphoma has recently been recognized as a novel variant of follicular lymphoma in the World Health Organization classification of lymphomas. Given the rarity of the disease, histopathological and genetic data on this type of lymphoma are still scarce. Design and MethodsWe analyzed 25 cases of pediatric follicular lymphoma (patients aged ≤18 years) by morphology, immunohistochemistry and interphase fluorescence in situ hybridization. All patients analyzed were treated within Non-Hodgkin's Lymphoma -Berlin-FrankfurtMünster (NHL-BFM) multicenter trials, and the cohort was representative of the German population. ResultsThe genetic hallmark of adult follicular lymphoma, t(14;18)(q32;q21), was not detectable in any of the pediatric cases, although BCL2 protein was expressed in 55% of the latter cases. No correlation was found between BCL2 protein expression and outcome. Chromosomal breaks in the immunoglobulin heavy chain gene (IGH) and the BCL6 locus were detected in 5 of 17 and 1 of 18 cases, respectively. Patients with pediatric follicular lymphoma had long event-free survival and, in contrast to adult follicular lymphoma, the clinical course was not dominated by relapses. A simultaneous diffuse large B-cell lymphoma was frequently detected at initial diagnosis in children but did not indicate an aggressive clinical course. ConclusionsOur data suggest that pediatric follicular lymphoma is a disease that differs from its adult counterpart both genetically and clinically.Key words: pediatric follicular lymphoma, childhood lymphoma, pediatric diffuse large B-cell lymphoma, t(14;18). NonHodgkin's Lymphoma -Berlin-Frankfurt-Münster (NHL-BFM) multicenter trials. Haematologica. 2010; 95:253-259. doi:10.3324/haematol.2009 This is an open-access paper. Citation: Oschlies I, Salaverria I, Mahn F, Meinhardt A, Zimmermann M, Woessmann W, Burkhardt B, Gesk S, Krams M, Reiter A, Siebert R, and Klapper W. Pediatric follicular lymphoma -a clinico-pathological study of a population-based series of patients treated within thePediatric follicular lymphoma -a clinico-pathological study of a population-based series of patients treated within the Non-Hodgkin's Lymphoma -Berlin-FrankfurtMünster (NHL-BFM) multicenter trials

Rituximab is active as a single-agent in pediatric B-NHL even though the RR was lower than requested in the phase II plan.