Metastatic Group 3 Medulloblastoma in a Patient With Tuberous Sclerosis Complex: Case Description and Molecular Characterization of the Tumor
Romina Moavero MD
Neuroscience and Neurorehabilitation Department, Neurology Unit, Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Systems Medicine Department, Child Neurology and Psychiatry Unit, Tor Vergata University Hospital of Rome, Rome, Italy
Search for more papers by this authorCorresponding Author
Valentina Folgiero MD, PhD
Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Correspondence to: Valentina Folgiero, Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy. E-mail: [email protected]Search for more papers by this authorAndrea Carai MD, PhD
Department of Neuroscience and Neurorehabilitation, Neurosurgery Unit, Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Search for more papers by this authorEvelina Miele MD, PhD
Department of Molecular Medicine, Sapienza University, Rome, Italy
Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia, Rome, Italy
Search for more papers by this authorElisabetta Ferretti MD,PhD
Department of Molecular Medicine, Sapienza University, Rome, Italy
Search for more papers by this authorAgnese Po PhD
Department of Molecular Medicine, Sapienza University, Rome, Italy
Search for more papers by this authorFrancesca Diomedi Camassei MD, PhD
Department of Laboratories – Pathology Unit Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Search for more papers by this authorFrancesca Romana Lepri PhD
Department of Laboratories, Medical Genetics laboratory, Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Search for more papers by this authorFederico Vigevano MD
Neuroscience and Neurorehabilitation Department, Neurology Unit, Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Search for more papers by this authorPaolo Curatolo MD
Systems Medicine Department, Child Neurology and Psychiatry Unit, Tor Vergata University Hospital of Rome, Rome, Italy
Search for more papers by this authorMassimiliano Valeriani MD
Neuroscience and Neurorehabilitation Department, Neurology Unit, Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Search for more papers by this authorGiovanna S. Colafati MD
Neuroradiology Unit, Imaging Department, Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Search for more papers by this authorFranco Locatelli MD
Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Department of Pediatric Science, University of Pavia, Italy
Search for more papers by this authorAssunta Tornesello MD
Department of Pediatrics, “Università Cattolica del Sacro Cuore,”, Rome, Italy
Search for more papers by this authorAngela Mastronuzzi MD
Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Search for more papers by this authorRomina Moavero MD
Neuroscience and Neurorehabilitation Department, Neurology Unit, Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Systems Medicine Department, Child Neurology and Psychiatry Unit, Tor Vergata University Hospital of Rome, Rome, Italy
Search for more papers by this authorCorresponding Author
Valentina Folgiero MD, PhD
Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Correspondence to: Valentina Folgiero, Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy. E-mail: [email protected]Search for more papers by this authorAndrea Carai MD, PhD
Department of Neuroscience and Neurorehabilitation, Neurosurgery Unit, Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Search for more papers by this authorEvelina Miele MD, PhD
Department of Molecular Medicine, Sapienza University, Rome, Italy
Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia, Rome, Italy
Search for more papers by this authorElisabetta Ferretti MD,PhD
Department of Molecular Medicine, Sapienza University, Rome, Italy
Search for more papers by this authorAgnese Po PhD
Department of Molecular Medicine, Sapienza University, Rome, Italy
Search for more papers by this authorFrancesca Diomedi Camassei MD, PhD
Department of Laboratories – Pathology Unit Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Search for more papers by this authorFrancesca Romana Lepri PhD
Department of Laboratories, Medical Genetics laboratory, Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Search for more papers by this authorFederico Vigevano MD
Neuroscience and Neurorehabilitation Department, Neurology Unit, Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Search for more papers by this authorPaolo Curatolo MD
Systems Medicine Department, Child Neurology and Psychiatry Unit, Tor Vergata University Hospital of Rome, Rome, Italy
Search for more papers by this authorMassimiliano Valeriani MD
Neuroscience and Neurorehabilitation Department, Neurology Unit, Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Search for more papers by this authorGiovanna S. Colafati MD
Neuroradiology Unit, Imaging Department, Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Search for more papers by this authorFranco Locatelli MD
Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Department of Pediatric Science, University of Pavia, Italy
Search for more papers by this authorAssunta Tornesello MD
Department of Pediatrics, “Università Cattolica del Sacro Cuore,”, Rome, Italy
Search for more papers by this authorAngela Mastronuzzi MD
Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital, , IRCCS, Rome, Italy
Search for more papers by this authorGrant sponsor: European Community; Grant number: 602391.
Conflict of interest: Nothing to declare.
Romina Moavero and Valentina Folgiero contributed equally to this work.
Abstract
Medulloblastoma is the most common pediatric brain tumor. We describe a child with tuberous sclerosis complex that developed a Group 3, myc overexpressed, metastatic medulloblastoma (MB). Considering the high risk of treatment-induced malignancies, a tailored therapy, omitting radiation, was given. Based on the evidence of mammalian target of rapamycin mTORC, mTOR Complex; RAS, Rat sarcoma; RAF, rapidly accelerated fibrosarcoma (mTOR) pathway activation in the tumor, targeted therapy was applied resulting in complete remission of disease. Although the PI3K/AKT/mTOR signaling pathway plays a role in MB, we did not find TSC1/TSC2 (TSC, tuberous sclerosis complex) mutation in our patient. We speculate that a different pathway resulting in mTOR activation is the basis of both TSC and MB in this child; H&E, haematoxilin and eosin; Gd, gadolinium.
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