{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:09:28Z","timestamp":1753877368586,"version":"3.41.2"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"vor","delay-in-days":55,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Recent large-scale genomic studies have revealed a spectrum of genetic variants associated with specific subtypes of central nervous system (CNS) tumors. The aim of this study was to determine the clinical utility of comprehensive genomic profiling of pediatric, adolescent and young adult (AYA) CNS tumors in a prospective setting, including detection of DNA sequence variants, gene fusions, copy number alterations (CNAs), and loss of heterozygosity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>OncoKids, a comprehensive DNA- and RNA-based next-generation sequencing (NGS) panel, in conjunction with chromosomal microarray analysis (CMA) was employed to detect diagnostic, prognostic, and therapeutic markers. NGS was performed on 222 specimens from 212 patients. Clinical CMA data were analyzed in parallel for 66% (146\/222) of cases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>NGS demonstrated clinically significant alterations in 66% (147\/222) of cases. Diagnostic markers were identified in 62% (138\/222) of cases. Prognostic information and targetable genomic alterations were identified in 22% (49\/222) and 18% (41\/222) of cases, respectively. Diagnostic or prognostic CNAs were revealed by CMA in 69% (101\/146) of cases. Importantly, clinically significant CNAs were detected in 57% (34\/60) of cases with noncontributory NGS results. Germline cancer predisposition testing was indicated for 27% (57\/212) of patients. Follow-up germline testing was performed for 20 patients which confirmed a germline pathogenic\/likely pathogenic variant in 9 cases: TP53 (2), NF1 (2), SMARCB1 (1), NF2 (1), MSH6 (1), PMS2 (1), and a patient with 47,XXY Klinefelter syndrome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our results demonstrate the significant clinical utility of integrating genomic profiling into routine clinical testing for pediatric and AYA patients with CNS tumors.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/noajnl\/vdab037","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T23:59:09Z","timestamp":1614297549000},"source":"Crossref","is-referenced-by-count":1,"title":["Clinical utility of comprehensive genomic profiling in central nervous system tumors of children and young adults"],"prefix":"10.1093","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4941-3538","authenticated-orcid":false,"given":"Jianling","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristiyana","family":"Kaneva","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Cancer and Blood Disease Institute and Department of Pediatrics, Children\u2019s Hospital Los Angeles, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew C","family":"Hiemenz","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Girish","family":"Dhall","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Cancer and Blood Disease Institute and Department of Pediatrics, Children\u2019s Hospital Los Angeles, Los Angeles, California, USA"},{"name":"Division of Pediatric Hematology-Oncology, University of Alabama at Birmingham, Birmingham, Alabama, USA"},{"name":"Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom Belle","family":"Davidson","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Cancer and Blood Disease Institute and Department of Pediatrics, Children\u2019s Hospital Los Angeles, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anat","family":"Erdreich-Epstein","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA"},{"name":"Division of Hematology-Oncology, Cancer and Blood Disease Institute and Department of Pediatrics, Children\u2019s Hospital Los Angeles, Los Angeles, California, USA"},{"name":"Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debra","family":"Hawes","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyle","family":"Hurth","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley S","family":"Margol","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Cancer and Blood Disease Institute and Department of Pediatrics, Children\u2019s Hospital Los Angeles, Los Angeles, California, USA"},{"name":"Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna J","family":"Mathew","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan J","family":"Robison","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Cancer and Blood Disease Institute and Department of Pediatrics, Children\u2019s Hospital Los Angeles, Los Angeles, California, USA"},{"name":"Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan J","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hung N","family":"Tran","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Los Angeles Medical Center, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander R","family":"Judkins","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer A","family":"Cotter","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA"},{"name":"Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaclyn 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