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      Precision oncogenomics in pediatrics: a personal reflection

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          Abstract

          Cindy Campbell, a bereaved parent who lost her son to a rare pediatric brain tumor, shares her experience and frustration over the lack of treatment options and minimal research funding in pediatric oncology. She invites Dr. Jeffrey P. Greenfield to reflect on the situation and share his professional experiences pertaining to advances in oncogenomics and pediatric brain tumors. They share a passion for making this technology available to all pediatric brain tumor patients in the future and using data to inform treatment protocols and improve outcomes.

          Most cited references4

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          The whole-genome landscape of medulloblastoma subtypes

          Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and ‘enhancer hijacking’ events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma. Supplementary information The online version of this article (doi:10.1038/nature22973) contains supplementary material, which is available to authorized users.
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            Long-Term Outcome of 4,040 Children Diagnosed With Pediatric Low-Grade Gliomas: An Analysis of the Surveillance Epidemiology and End Results (SEER) Database

            Background Children with pediatric low-grade gliomas (PLGG) are known to have excellent 10-year survival rates; however the outcomes of adult survivors of PLGG are unknown. We identified patients diagnosed with PLGG diagnosed between 1973 and 2008 through the Surveillance Epidemiology and End Results (SEER) database to examine outcomes of adult survivors of PLGG. Procedure Four thousand and forty patients with either WHO grade I or II PLGG were identified and outcome data retrieved. Two analyses were performed to assess survival and risk of death from tumor. Competing risks analysis was conducted and cumulative incidence curves of death due to disease were generated. Cox proportional hazards regression was performed, with adjustment for non-disease death. Kaplan–Meier curves for overall cancer specific survival (OS) were also generated. Results The 20-year OS was 87% ± 0.8% and the 20-year cumulative incidence of death due to glioma was 12% ± 0.8%. The incidence of death after transition to adulthood (age greater than 22 years) was slightly lower, with 20-year cumulative incidence of disease death of 7% ± 1.8%. Year of diagnosis, age of diagnosis, histology, WHO grade, primary site, radiation, and degree of initial resection were prognostic in univariate analysis, while the administration of radiation was the greatest risk of death in multivariate analysis of OS (hazard ratio = 3.9). Conclusions PLGGs are associated with an excellent long-term survival, with a low likelihood of PLGG related death in adult survivors. Treatment strategies for pediatric tumors should therefore aim for disease control during childhood and adolescence with an emphasis on minimizing long-term treatment induced toxicities.
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              Review of molecular classification and treatment implications of pediatric brain tumors

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                Author and article information

                Journal
                Cold Spring Harb Mol Case Stud
                Cold Spring Harb Mol Case Stud
                cshmcs
                cshmcs
                cshmcs
                Cold Spring Harbor Molecular Case Studies
                Cold Spring Harbor Laboratory Press
                2373-2873
                April 2018
                : 4
                : 2
                : a002865
                Affiliations
                [1 ]Ty Louis Campbell Foundation for Childhood Cancer Research, Carmel, New York 10512, USA;
                [2 ]Vice Chair for Academic Affairs in the Department of Neurological Surgery, Weill Cornell Medicine, New York, New York 10065, USA
                Author notes
                [3]

                Blogger at SuperTy.org

                Corresponding author: ccampbell@ 123456superty.org
                Article
                MCS002865Cam
                10.1101/mcs.a002865
                5880271
                29610396
                0e79f5d2-584e-447b-af10-621ec8d78b9e
                © 2018 Campbell and Greenfield; Published by Cold Spring Harbor Laboratory Press

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License, which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited.

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                Pages: 6
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