Pancreatoblastoma is a rare pediatric pancreatic malignancy for which the molecular pathogenesis is not understood. In this study, we report the findings of an integrated multiomics study of whole-exome and RNA sequencing as well as genome-wide copy number and methylation analyses of ten pancreatoblastoma cases. The pancreatoblastoma genome was characterized by a high frequency of aberrant activation of the Wnt signaling pathway, either via somatic mutations of (90%) and copy-neutral loss of heterozygosity (CN-LOH) of (10%). In addition, imprinting dysregulation of as a consequence of CN-LOH (80%), gain of paternal allele (10%), and gain of methylation (10%) was universally detected. At the transcriptome level, pancreatoblastoma exhibited an expression profile characteristic of early pancreas progenitor-like cells along with upregulation of the R-spondin/LGR5/RNF43 module. Our results offer a comprehensive description of the molecular basis for pancreatoblastoma and highlight rational therapeutic targets for its treatment. Molecular genetic analysis of a rare untreatable pediatric tumor reveals Wnt/IGF2 aberrations and features of early pancreas progenitor-like cells, suggesting cellular origins and rational strategies for therapeutic targeting. .
The cumulative incidence of secondary cancers in children in Japan was not high; however, the SIR was relatively high. Retinoblastoma or sarcoma in addition to allogeneic stem cell transplantation were significant risk factors for secondary cancers.
The role of diffusion weighted imaging and apparent diffusion coefficient in intracranial germ cell tumors has not been fully elucidated. The aim of this study was to evaluate whether the ADC correlates with the histologic subtypes of germ cell tumors. We also aimed to investigate whether the ADC values can predict treatment response. The authors retrospectively analyzed the ADC values of the enhancing and solid regions of germ cell tumors. The absolute ADC values and the normalized ADC values were compared among different histologic diagnoses. The ADC values before and after the first course of chemotherapy were also compared between the different prognostic groups. Ten patients were included in the study. The median age at diagnosis was 9.3 years (range 5.3-13.8 years). There were four patients with germinoma and six patients with nongerminomatous germ cell tumor (NGGCT) including five mixed germ cell tumors and one immature teratoma. The mean absolute and normalized ADC values (×10(-3) mm(2)/s) were significantly lower in germinomas [0.835 ± 0.065 (standard deviation) and 1.11 ± 0.096, respectively] than in NGGCTs (1.271 ± 0.145 and 1.703 ± 0.223, respectively) (p = 0.01). The ADC values before and after the first course of chemotherapy were available in four patients. The ADC value after the first chemotherapy had a tendency to increase more in patients who eventually demonstrated complete response with chemotherapy than in patients who required second-look surgery. Assessment of the ADC values of germ cell tumors is considered to facilitate differentiation of histological subtypes of germ cell tumors. Evaluation of the ADC may also be useful for predicting treatment response.
In addition to BCR, various rare fusion partners for the ABL1 gene have been reported in leukemia. We have identified the fusion gene SNX2-ABL1 in a pediatric case of acute lymphoblastic leukemia (ALL), which has only once previously been reported in an adult patient. Cytogenetic analysis detected this fusion gene arising from a t(5;9)(q22;q34) translocation. ALL cells carrying a SNX2-ABL1 fusion exhibited a BCR-ABL1+ ALL-like gene expression profile. The patient poorly responded to dasatinib but partially responded to imatinib. Treatment using tyrosine kinase inhibitors requires further investigation to optimize the genotype-based treatment stratification for patients with SNX2-ABL1 fusion.
The Japan Society of Clinical Oncology (JSCO) published the “JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients” in 2017. This was the first guideline in cancer reproductive medicine in Japan. In the field of cancer reproductive medicine, close cooperation between an oncologist and a physician for reproductive medicine is important from before treatment initiation until long after treatment. The guideline takes into consideration disease specificity and provides opinions from the perspective of oncologists and specialists in reproductive medicine that are in line with the current state of the Japanese medical system. It is intended to serve as a reference for medical staff in both fields regarding the availability of fertility preservation therapy before the start of cancer treatment. Appropriate use of this guideline makes it easier to determine whether fertility preservation therapy is feasible and, ultimately, to improve survivorship in childhood, adolescent, and young adult cancer patients. In this article (Part 2), we describe details by organ/system and also for pediatric cancer.
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