The Pediatric Cancer Genome Project

St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project, Memphis, Tennessee, USA.
Nature Genetics (Impact Factor: 29.65). 08/2012; 44(6):619-22. DOI: 10.1038/ng.2287
Source: PubMed
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    ABSTRACT: The present study describes the recent advances in the identification of targetable genomic alterations in pediatric cancers, along with the progress and associated challenges in translating these findings into therapeutic benefit. Each field within pediatric cancer has rapidly and comprehensively begun to define genomic targets in tumors that potentially can improve the clinical outcome of patients, including hematologic malignancies (leukemia and lymphoma), solid malignancies (neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma), and brain tumors (gliomas, ependymomas, and medulloblastomas). Although each tumor has specific and sometimes overlapping genomic targets, the translation to the clinic of new targeted trials and precision medicine protocols is still in its infancy. The first clinical tumor profiling studies in pediatric oncology have demonstrated the feasibility and patient enthusiasm for the personalized medicine paradigm, but have yet to demonstrate clinical utility. Complexities influencing implementation include rapidly evolving sequencing technologies, tumor heterogeneity, and lack of access to targeted therapies. The return of incidental findings from the germline also remains a challenge, with evolving policy statements and accepted standards. The translation of genomic discoveries to the clinic in pediatric oncology continues to move forward at a brisk pace. Early adoption of genomics for tumor classification, risk stratification, and initial trials of targeted therapeutic agents has led to powerful results. As our experience grows in the integration of genomic and clinical medicine, the outcome for children with cancer should continue to improve.
    Current Opinion in Pediatrics 12/2014; 27(1). DOI:10.1097/MOP.0000000000000172 · 2.74 Impact Factor
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    ABSTRACT: The past 2 decades have witnessed a revolution in the management of childhood brain tumors, with the establishment of multidisciplinary teams and national and international consortiums that led to significant improvements in the outcomes of children with brain tumors. Unprecedented cooperation within the pediatric neuro-oncology community and sophisticated rapidly evolving technology have led to advances that are likely to revolutionize treatment strategies and improve outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.
    Pediatric Clinics of North America 02/2015; 62(1):167-178. DOI:10.1016/j.pcl.2014.09.011 · 2.20 Impact Factor
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    ABSTRACT: Introducing whole genome sequencing (WGS) into pediatric cancer research at diagnosis poses unique challenges related to informed consent. WGS requires tissue obtained prior to initiating treatment, when families may be overwhelmed with uncertainty and fear. Motivation to participate may be high without fully understanding the range of possible results, including secondary findings. Little is known about parental knowledge, attitudes, and beliefs about this type of research. A qualitative study was conducted to investigate parental knowledge about genetic concepts and WGS, thoughts about the informed consent process, and preferences for secondary findings. Focus groups were conducted with parents/guardians of children with cancer and semi-structured interviews were conducted in a control group without cancer. All transcripts were analyzed using content analysis. Four focus groups included 15 participants; eight semi-structured interviews included 10 participants. Basic knowledge about genetics was limited to heredity. Some knowledge of genomic analysis was present in 3/15 focus group participants. Major factors related to participation in WGS research were: (i) hope for their child and future children; (ii) no additional procedures; (iii) and protection of privacy. All favored a two-step consent process, first to store extra tissue from a diagnostic biopsy/resection, followed by consenting to WGS research, one-to-two months later. The desire to receive secondary findings was high among both groups, but there were individuals who did not want these results, fearing increased anxiety. Parents/guardians of children with cancer have limited knowledge about WGS. A two-step consent process may improve their ability to provide meaningful informed consent. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 04/2015; DOI:10.1002/pbc.25520 · 2.56 Impact Factor


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