LOGGIC Core BioClinical Data Bank: Added clinical value of RNA-Seq in an international molecular diagnostic registry for pediatric low-grade glioma patients
Por:
Hardin EC, Schmid S, Sommerkamp A, Bodden C, Heipertz AE, Sievers P, Wittmann A, Milde T, Pfister SM, von Deimling A, Horn S, Herz NA, Simon M, Perera AA, Azizi A, Cruz-Martínez O, Curry S, Van Damme A, Garami M, Hargrave D, Kattamis A, Kotnik BF, Lähteenmäki P, Scheinemann K, Schouten-van Meeteren AYN, Sehested A, Viscardi E, Wormdal OM, Zapotocky M, Ziegler DS, Koch A, Driever PH, Witt O, Capper D, Sahm F, Jones DTW and van Tilburg CM
Publicada:
2 nov 2023
Ahead of Print:
1 may 2023
Resumen:
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.
Filiaciones:
Hardin EC:
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK)
Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany
Heidelberg Medical Faculty, University of Heidelberg, Germany
National Center for Tumor Diseases (NCT), Heidelberg, Germany
Schmid S:
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neuropathology, Berlin, Germany
Sommerkamp A:
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
National Center for Tumor Diseases (NCT), Heidelberg, Germany
Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
Bodden C:
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK)
National Center for Tumor Diseases (NCT), Heidelberg, Germany
Heipertz AE:
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK)
Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany
Heidelberg Medical Faculty, University of Heidelberg, Germany
National Center for Tumor Diseases (NCT), Heidelberg, Germany
Sievers P:
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany
Wittmann A:
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
National Center for Tumor Diseases (NCT), Heidelberg, Germany
Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
Milde T:
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK)
Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany
National Center for Tumor Diseases (NCT), Heidelberg, Germany
Pfister SM:
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany
National Center for Tumor Diseases (NCT), Heidelberg, Germany
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
von Deimling A:
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany
Horn S:
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, HIT-LOGGIC German Registry for children and adolescents with low-grade glioma, Berlin, Germany
Herz NA:
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, HIT-LOGGIC German Registry for children and adolescents with low-grade glioma, Berlin, Germany
Simon M:
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, HIT-LOGGIC German Registry for children and adolescents with low-grade glioma, Berlin, Germany
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Oncology/Hematology, Berlin, Germany
Perera AA:
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
Heidelberg Medical Faculty, University of Heidelberg, Germany
National Center for Tumor Diseases (NCT), Heidelberg, Germany
Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
Azizi A:
Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
Cruz-Martínez O:
Neuro-Oncology Unit, Pediatric Cancer Center, Hospital Sant Joan de Deu, Barcelona, Spain
Curry S:
Department of Haematology & Oncology, Children's Health Ireland at Crumlin, Dublin, Ireland
Van Damme A:
Department of Pediatric Hematology and Oncology, Saint Luc University Hospital, Brussels, Belgium
Garami M:
2nd Department of Pediatrics, Semmelweis University, 1094 Budapest, Hungary
Hargrave D:
Great Ormond Street Hospital for Children NHS Trust London, London, UK
Kattamis A:
First Department of Paediatrics, "Aghia Sophia" Children's Hospital, National and Kapodistrian University of Athens, Athens 11527, Greece
Kotnik BF:
University Medical Centre Ljubljana (UMC), University Children's Hospital, Department of Haematology and Oncology, Ljubljana, Slovenia
Lähteenmäki P:
Turku University and University Hospital, FI20521 Turku, Finland
Swedish Childhood Cancer Registry, Karolinska Institutet, Stockholm, Sweden
Scheinemann K:
Division of Pediatric Oncology - Hematology, Department of Pediatrics, Kantonsspital Aarau, Aarau, Switzerland
Department of Health Sciences and Medicine, University of Lucerne, Switzerland
Department of Paediatrics, McMaster Children's Hospital and McMaster University, Hamilton, Canada
Schouten-van Meeteren AYN:
Department of Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands
Sehested A:
Department of Paediatrics and Adolescent Medicine, The University Hospital Rigshospitalet, Copenhagen, Denmark
Viscardi E:
Pediatric Oncology Unit, Padova University, Padova, Italy
Wormdal OM:
Section of Pediatric Oncology, UNN University Hospital of Northern Norway, Tromsø, Norway
Zapotocky M:
Department of Pediatric Hematology and Oncology, Second Faculty of Medicine, University Hospital Motol, Charles University, Prague, Czech Republic
Ziegler DS:
Kids Cancer Centre, Sydney Children's Hospital, High St, Randwick, NSW, Australia
Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, Australia
School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Sydney, NSW, Australia
Koch A:
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neuropathology, Berlin, Germany
Driever PH:
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, HIT-LOGGIC German Registry for children and adolescents with low-grade glioma, Berlin, Germany
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Oncology/Hematology, Berlin, Germany
Witt O:
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK)
Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany
National Center for Tumor Diseases (NCT), Heidelberg, Germany
Capper D:
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neuropathology, Berlin, Germany
German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany
Sahm F:
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany
Jones DTW:
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
National Center for Tumor Diseases (NCT), Heidelberg, Germany
Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
van Tilburg CM:
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK)
Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany
National Center for Tumor Diseases (NCT), Heidelberg, Germany
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