Stefan Schönberger1,2, Mahsa Mir Mohseni3, Jörg Ellinger4, Giao Vu Quynh Tran3, Martina Becker5, Alexander Claviez6, Carl-Friedrich Classen7, Barbara Hermes8, Pablo Hernáiz Driever9, Norbert Jorch10, Melchior Lauten11, Marcus Mehlitz12, Niklas Schäfer13, Johanna Scheer-Preiss14, Dominik T Schneider15, Anja Troeger16, Gabriele Calaminus3, Dagmar Dilloo3. 1. Department of Pediatric Hematology and Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany. stefan.schoenberger@uk-essen.de. 2. Department of Pediatric Hematology and Oncology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany. stefan.schoenberger@uk-essen.de. 3. Department of Pediatric Hematology and Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany. 4. Department of Urology and Center of Integrated Oncology (CIO), University Hospital Bonn, Bonn, Germany. 5. Department of Pediatric Hematology and Oncology, Goethe University Frankfurt, Frankfurt, Germany. 6. Department of Pediatrics, Pediatric Hematology and Oncology, Medical University of Schleswig-Holstein, Campus Kiel, Kiel, Germany. 7. University Children's and Adolescents' Hospital, Rostock University Medical Center, Rostock, Germany. 8. Kreiskliniken Reutlingen, Medizinische Klinik I, Reutlingen, Germany. 9. Department of Pediatric Oncology and Hematology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany. 10. Department of Pediatric Hematology and Oncology, Hospital of Bielefeld, Bielefeld, Germany. 11. Department of Pediatric and Adolescent Medicine, Pediatric Hematology and Oncology, University Hospital Schleswig-Holstein, Lübeck, Germany. 12. Department of Neurosurgery, Krankenhaus der Barmherzigen Brüder Trier, Trier, Germany. 13. Division of Clinical Neurooncology, Department of Neurology and Center of Integrated Oncology (CIO), University of Bonn, Bonn, Germany. 14. Department of Pediatric and Adolescent Medicine, Braunschweig Municipal Hospital, Brunswick, Germany. 15. Clinic of Pediatrics, Dortmund Municipal Hospital, Dortmund, Germany. 16. Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Hospital Regensburg, Regensburg, Germany.
Abstract
PURPOSE: Intracranial germ cell tumors (iGCT) comprise germinoma and non-germinoma. Their diagnosis predominantly relies on biopsy as only one-fifth of patients present with elevated biomarkers (AFP/ß-HCG) in serum or cerebrospinal fluid (CSF). MicroRNAs (miR/miRNA) have emerged as non-invasive biomarkers in extracranial GCT and may potentially facilitate non-invasive diagnosis in iGCT. METHODS: We analyzed eight miRNAs in serum and CSF from the miR-371~373- and miR-302/367-clusters and four miRNAs differentially expressed in iGCT tissue (miR-142-5p/miR-146a-5p/miR-335-5p/miR-654-3p) from eight iGCT patients (age 10-33 years) and 12 control subjects by pre-amplified RT-qPCR. MiR-30b-5p (serum) and miR-204-5p (CSF) acted as reference genes. ΔCt-values were expressed as [Formula: see text] after standardization against controls. RESULTS: Between iGCT and control patients' serum ΔCt-values of miR-371a-3p (p = 0.0159), miR-372-3p (p= 0.0095, miR-367 (p = 0.0190), miR-302a (p = 0.0381) and miR-302d-3p (p = 0.0159) differed significantly. Discriminatory pattern in CSF was similar to serum as miR-371a (p = 0.0286), miR-372-3p (p = 0.0028), miR-367-3p (p = 0.0167) and miR-302d-3p (p = 0.0061) distinguished between patients and controls. Abundant [Formula: see text] levels of each of these miRNAs were found across all serum and CSF samples including biomarker-negative patients. CONCLUSION: With the largest data set so far, we underline the suitability of miR-371a, miR-372, miR-367 and miR-302d in serum and CSF for diagnosis of iGCT, particularly in biomarker-negative germinoma. Diagnosis of iGCT by miRNA analysis is a feasible and valid approach, particularly as serum can be readily obtained by a less invasive procedure. MiRNA analysis may discriminate iGCT from other tumors with similar radiological findings and may allow to monitor response to therapy as well as early relapse during follow-up.
PURPOSE: Intracranial germ cell tumors (iGCT) comprise germinoma and non-germinoma. Their diagnosis predominantly relies on biopsy as only one-fifth of patients present with elevated biomarkers (AFP/ß-HCG) in serum or cerebrospinal fluid (CSF). MicroRNAs (miR/miRNA) have emerged as non-invasive biomarkers in extracranial GCT and may potentially facilitate non-invasive diagnosis in iGCT. METHODS: We analyzed eight miRNAs in serum and CSF from the miR-371~373- and miR-302/367-clusters and four miRNAs differentially expressed in iGCT tissue (miR-142-5p/miR-146a-5p/miR-335-5p/miR-654-3p) from eight iGCT patients (age 10-33 years) and 12 control subjects by pre-amplified RT-qPCR. MiR-30b-5p (serum) and miR-204-5p (CSF) acted as reference genes. ΔCt-values were expressed as [Formula: see text] after standardization against controls. RESULTS: Between iGCT and control patients' serum ΔCt-values of miR-371a-3p (p = 0.0159), miR-372-3p (p= 0.0095, miR-367 (p = 0.0190), miR-302a (p = 0.0381) and miR-302d-3p (p = 0.0159) differed significantly. Discriminatory pattern in CSF was similar to serum as miR-371a (p = 0.0286), miR-372-3p (p = 0.0028), miR-367-3p (p = 0.0167) and miR-302d-3p (p = 0.0061) distinguished between patients and controls. Abundant [Formula: see text] levels of each of these miRNAs were found across all serum and CSF samples including biomarker-negative patients. CONCLUSION: With the largest data set so far, we underline the suitability of miR-371a, miR-372, miR-367 and miR-302d in serum and CSF for diagnosis of iGCT, particularly in biomarker-negative germinoma. Diagnosis of iGCT by miRNA analysis is a feasible and valid approach, particularly as serum can be readily obtained by a less invasive procedure. MiRNA analysis may discriminate iGCT from other tumors with similar radiological findings and may allow to monitor response to therapy as well as early relapse during follow-up.
Authors: G Calaminus; M Bamberg; M C Baranzelli; Y Benoit; L C di Montezemolo; F Fossati-Bellani; H Jürgens; H J Kühl; H G Lenard; M L Curto Journal: Neuropediatrics Date: 1994-02 Impact factor: 1.947
Authors: Klaus-Peter Dieckmann; Arlo Radtke; Lajos Geczi; Cord Matthies; Petra Anheuser; Ulrike Eckardt; Jörg Sommer; Friedemann Zengerling; Emanuela Trenti; Renate Pichler; Hanjo Belz; Stefan Zastrow; Alexander Winter; Sebastian Melchior; Johannes Hammel; Jennifer Kranz; Marius Bolten; Susanne Krege; Björn Haben; Wolfgang Loidl; Christian Guido Ruf; Julia Heinzelbecker; Axel Heidenreich; Jann Frederik Cremers; Christoph Oing; Thomas Hermanns; Christian Daniel Fankhauser; Silke Gillessen; Hermann Reichegger; Richard Cathomas; Martin Pichler; Marcus Hentrich; Klaus Eredics; Anja Lorch; Christian Wülfing; Sven Peine; Werner Wosniok; Carsten Bokemeyer; Gazanfer Belge Journal: J Clin Oncol Date: 2019-03-15 Impact factor: 44.544