Clinical utility of comprehensive genomic profiling in central nervous system tumors of children and young adults.

CNS tumors NGS oncology panel NTRK QKI–RAF1 chromosomal microarray analysis

Journal

Neuro-oncology advances
ISSN: 2632-2498
Titre abrégé: Neurooncol Adv
Pays: England
ID NLM: 101755003

Informations de publication

Date de publication:
Historique:
entrez: 5 5 2021
pubmed: 6 5 2021
medline: 6 5 2021
Statut: epublish

Résumé

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. 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. 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: Our results demonstrate the significant clinical utility of integrating genomic profiling into routine clinical testing for pediatric and AYA patients with CNS tumors.

Sections du résumé

BACKGROUND BACKGROUND
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.
METHODS METHODS
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.
RESULTS RESULTS
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:
CONCLUSIONS CONCLUSIONS
Our results demonstrate the significant clinical utility of integrating genomic profiling into routine clinical testing for pediatric and AYA patients with CNS tumors.

Identifiants

DOI: 10.1093/noajnl/vdab037 PMID: 33948563 PMC: PMC8080244
pubmed: 33948563
doi: 10.1093/noajnl/vdab037
pii: vdab037
pmc: PMC8080244
doi:

Types de publication

Journal Article

Langues

eng

Pagination

vdab037

Subventions

Organisme : NCI NIH HHS
ID : P50 CA211015
Pays : United States

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.

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Auteurs

Jianling Ji (J)

Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA.
ORCID: 0000-0003-4941-3538

Kristiyana Kaneva (K)

Division of Hematology-Oncology, Cancer and Blood Disease Institute and Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, USA.

Matthew C Hiemenz (MC)

Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

Girish Dhall (G)

Division of Hematology-Oncology, Cancer and Blood Disease Institute and Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, USA.
Division of Pediatric Hematology-Oncology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Tom Belle Davidson (TB)

Division of Hematology-Oncology, Cancer and Blood Disease Institute and Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, USA.

Anat Erdreich-Epstein (A)

Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA.
Division of Hematology-Oncology, Cancer and Blood Disease Institute and Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, USA.
Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Debra Hawes (D)

Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

Kyle Hurth (K)

Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

Ashley S Margol (AS)

Division of Hematology-Oncology, Cancer and Blood Disease Institute and Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, USA.
Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Anna J Mathew (AJ)

Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

Nathan J Robison (NJ)

Division of Hematology-Oncology, Cancer and Blood Disease Institute and Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, USA.
Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Ryan J Schmidt (RJ)

Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

Hung N Tran (HN)

Kaiser Permanente Los Angeles Medical Center, Los Angeles, California, USA.

Alexander R Judkins (AR)

Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

Jennifer A Cotter (JA)

Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA.
Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Jaclyn A Biegel (JA)

Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA.
Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Classifications MeSH