LOGGIC Core BioClinical Data Bank: Added clinical value of RNA-Seq in an international molecular diagnostic registry for pediatric low-grade glioma patients

Emily C Hardin, Simone Schmid, Alexander Sommerkamp, Carina Bodden, Anna-Elisa Heipertz, Philipp Sievers, Andrea Wittmann, Till Milde, Stefan M Pfister, Andreas von Deimling, Svea Horn, Nina A Herz, Michèle Simon, Ashwyn A Perera, Amedeo Azizi, Ofelia Cruz, Sarah Curry, An Van Damme, Miklos Garami, Darren HargraveAntonis Kattamis, Barbara Faganel Kotnik, Päivi Lähteenmäki, Katrin Scheinemann, Antoinette Y N Schouten-van Meeteren, Astrid Sehested, Elisabetta Viscardi, Ole Mikal Wormdal, Michal Zapotocky, David S Ziegler, Arend Koch, Pablo Hernáiz Driever, Olaf Witt, David Capper, Felix Sahm, David T W Jones, Cornelis M van Tilburg*

*Corresponding author af dette arbejde
7 Citationer (Scopus)


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.

Udgave nummer11
Sider (fra-til)2087-2097
Antal sider11
StatusUdgivet - 2 nov. 2023


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