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LOGGIC Core BioClinical Data Bank: Added clinical value of RNA-Seq in an international molecular diagnostic registry for pediatric low-grade glioma patients
EC. Hardin, S. Schmid, A. Sommerkamp, C. Bodden, AE. Heipertz, P. Sievers, A. Wittmann, T. Milde, SM. Pfister, A. von Deimling, S. Horn, NA. Herz, M. Simon, AA. Perera, A. Azizi, O. Cruz, S. Curry, A. Van Damme, M. Garami, D. Hargrave, A....
Language English Country England, Great Britain
Document type Multicenter Study, Journal Article
Grant support
Brain Tumour Charity
HIT-LOGGIC
Pediatric Brain Tumor Foundation
Deutsche Kinderkrebsstiftung
NLK
Free Medical Journals
from 1999 to 1 year ago
PubMed Central
from 1999 to 1 year ago
Europe PubMed Central
from 1999 to 1 year ago
Open Access Digital Library
from 1999-01-01
Medline Complete (EBSCOhost)
from 2004-01-01 to 1 year ago
- MeSH
- Child MeSH
- DNA-Binding Proteins genetics MeSH
- Glioma * pathology MeSH
- Precision Medicine MeSH
- Humans MeSH
- Pathology, Molecular MeSH
- Proto-Oncogene Proteins B-raf * genetics MeSH
- Proto-Oncogene Proteins genetics MeSH
- RNA-Seq MeSH
- Transcription Factors genetics MeSH
- Protein-Tyrosine Kinases MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
BACKGROUND: The international, multicenter registry LOGGIC Core BioClinical Data Bank aims to enhance the understanding of tumor biology in pediatric low-grade glioma (pLGG) and provide clinical and molecular data to support treatment decisions and interventional trial participation. Hence, the question arises whether implementation of RNA sequencing (RNA-Seq) using fresh frozen (FrFr) tumor tissue in addition to gene panel and DNA methylation analysis improves diagnostic accuracy and provides additional clinical benefit. METHODS: Analysis of patients aged 0 to 21 years, enrolled in Germany between April 2019 and February 2021, and for whom FrFr tissue was available. Central reference histopathology, immunohistochemistry, 850k DNA methylation analysis, gene panel sequencing, and RNA-Seq were performed. RESULTS: FrFr tissue was available in 178/379 enrolled cases. RNA-Seq was performed on 125 of these samples. We confirmed KIAA1549::BRAF-fusion (n = 71), BRAF V600E-mutation (n = 12), and alterations in FGFR1 (n = 14) as the most frequent alterations, among other common molecular drivers (n = 12). N = 16 cases (13%) presented rare gene fusions (eg, TPM3::NTRK1, EWSR1::VGLL1, SH3PXD2A::HTRA1, PDGFB::LRP1, GOPC::ROS1). In n = 27 cases (22%), RNA-Seq detected a driver alteration not otherwise identified (22/27 actionable). The rate of driver alteration detection was hereby increased from 75% to 97%. Furthermore, FGFR1 internal tandem duplications (n = 6) were only detected by RNA-Seq using current bioinformatics pipelines, leading to a change in analysis protocols. CONCLUSIONS: The addition of RNA-Seq to current diagnostic methods improves diagnostic accuracy, making precision oncology treatments (MEKi/RAFi/ERKi/NTRKi/FGFRi/ROSi) more accessible. We propose to include RNA-Seq as part of routine diagnostics for all pLGG patients, especially when no common pLGG alteration was identified.
2nd Department of Pediatrics Semmelweis University Budapest Hungary
Children's Cancer Institute Lowy Cancer Research Centre UNSW Sydney Sydney Australia
Clinical Cooperation Unit Neuropathology German Cancer Research Center Heidelberg Germany
Clinical Cooperation Unit Pediatric Oncology German Cancer Research Center Heidelberg Germany
Department of Haematology and Oncology Children's Health Ireland at Crumlin Dublin Ireland
Department of Health Sciences and Medicine University of Lucerne Lucerne Switzerland
Department of Paediatrics McMaster Children's Hospital and McMaster University Hamilton Canada
Department of Pediatric Hematology and Oncology Saint Luc University Hospital Brussels Belgium
Department of Pediatric Oncology Princess Máxima Center for Pediatric Oncology Utrecht Netherlands
Division of Pediatric Glioma Research German Cancer Research Center Heidelberg Germany
Division of Pediatric Neurooncology German Cancer Research Center Heidelberg Germany
German Cancer Consortium Heidelberg Germany
Great Ormond Street Hospital for Children NHS Trust London London UK
Heidelberg Medical Faculty University of Heidelberg Heidelberg Germany
Hopp Children's Cancer Center Heidelberg Heidelberg Germany
Kids Cancer Centre Sydney Children's Hospital High St Randwick NSW Australia
National Center for Tumor Diseases Heidelberg Germany
Neuro Oncology Unit Pediatric Cancer Center Hospital Sant Joan de Deu Barcelona Spain
Pediatric Oncology Unit Padova University Padova Italy
School of Clinical Medicine UNSW Medicine and Health UNSW Sydney Sydney NSW Australia
Section of Pediatric Oncology UNN University Hospital of Northern Norway Tromsø Norway
Swedish Childhood Cancer Registry Karolinska Institutet Stockholm Sweden
References provided by Crossref.org
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